DOCSLIB.ORG

Transplanted Thymus Thymus Nor the Development of Impairs Neither the Recovery of Recipient Depleted Lymphocyte Infusion

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Transplanted Thymus Thymus Nor the Development of Impairs Neither the Recovery of Recipient Depleted Lymphocyte Infusion CD4+ T Cell −Depleted Lymphocyte Infusion Impairs Neither the Recovery of Recipient Thymus nor the Development of Transplanted Thymus This information is current as of September 26, 2021. Ming Shi, Ming Li, Yunze Cui, Lin Liu, Yasushi Adachi and Susumu Ikehara J Immunol 2013; 190:2976-2983; Prepublished online 4 February 2013; doi: 10.4049/jimmunol.1201605 Downloaded from http://www.jimmunol.org/content/190/6/2976 Supplementary http://www.jimmunol.org/content/suppl/2013/02/04/jimmunol.120160 http://www.jimmunol.org/ Material 5.DC1 References This article cites 36 articles, 10 of which you can access for free at: http://www.jimmunol.org/content/190/6/2976.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision by guest on September 26, 2021 • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Author Choice Freely available online through The Journal of Immunology Author Choice option Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2013 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology CD4+ T Cell–Depleted Lymphocyte Infusion Impairs Neither the Recovery of Recipient Thymus nor the Development of Transplanted Thymus Ming Shi,* Ming Li,* Yunze Cui,*,† Lin Liu,* Yasushi Adachi,*,‡ and Susumu Ikehara* Thymus transplantation, in conjunction with bone marrow transplantation (BMT), has been attracting attention for the treatment of various diseases. Recently, donor lymphocyte infusion (DLI) has been used as a helpful tool for establishing donor chimerism and preventing a relapse of leukemia/lymphoma. However, the effects of DLI on transplanted and recipient thymuses have not been explored. We therefore performed DLI in the intrabone marrow–BMT + thymus transplantation setting. We have found that DLI leads to derangements in both recipient thymuses and transplanted thymuses; by 2 wk after BMT, we saw a decrease in total cell number, a lower percentage of CD4+CD8+ cells, and the obliteration of the thymic corticomedullary junction. Four weeks later, the Downloaded from thymic impairment became more serious. However, when we depleted the CD4+ T cells (CD42-DLI), the recipient thymic recovery and transplanted thymic development were significantly restored by the treatment. In addition, there were much greater levels of TNF-a and Fas ligand, and a lower percentage of regulatory T cells in the DLI group than in the CD42-DLI group. These findings indicate that inflammation induced by DLI, especially by CD4+ T cells, plays a crucial role in the thymic impairment. The Journal of Immunology, 2013, 190: 2976–2983. http://www.jimmunol.org/ llogeneic bone marrow transplantation (allo-BMT) is chronic GvHD (13). Thymus transplantation (TT), an attractive a potentially curative therapy for certain diseases of the method for improving T cell functions, has been applied clinically A hematopoietic system, immunodeficiencies, autoimmune for patients with DiGeorge syndrome or HIV infection, which diseases, solid malignant tumors, and so on (1–6). We have developed elicits the hypoplasia of the thymus (14). However, in mice, al- a new and powerful bone marrow transplantation (BMT) method: though T cell functions were restored or enhanced by TT, no con- intrabone marrow–BMT (IBM-BMT) (7), in which donor bone comitant GvHD was observed after TT in conjunction with allo- marrow cells (BMCs) are directly injected into the recipient’s bone BMT (15). Therefore, TT can be used to treat autoimmune diseases marrow cavity. Therefore, a much greater number of donor hemato- in chimeric-resistant MRL/lpr mice and type 2 diabetes mellitus, poietic stem cells and mesenchymal stromal cells (including mesen- and to suppress tumor growth (16–18). by guest on September 26, 2021 chymal stem cells) can be inoculated into the recipient bone marrow Donor lymphocyte infusion (DLI) is often used after allo-BMT by IBM-BMT than by conventional i.v. BMT. This results in the rapid to prevent disease relapse in the setting of T cell–depleted BMT or reconstitution of donor hematopoietic cells and permits a reduction nonmyeloablative conditioning regimens. It is also a combined in the doses of irradiation used as a conditioning regimen (8–10). method to convert from mixed chimerism to full donor chimerism The thymus is an organ for inducing T cells and maintaining (19, 20). However, DLI-induced GvHD is always associated with homeostasis. However, thymic functions are impaired by the con- an increase in therapy-related morbidity because of its uncon- ditioning regimen and the acute graft-versus-host disease (GvHD) trollable and fatal characteristics (21). It has been reported that that occurs after allo-BMT, resulting in deficient cell immunity (11, many factors are involved in the damage to the recipient thymus 12). In addition, there is a strong association between posttrans- after DLI (22, 23), whereas the effects of DLI on the transplanted plant autoimmune disease and the thymic dysfunction caused by thymus have hitherto remained unexplored. In this study, we investigate the influence of DLI on both re- *Department of Stem Cell Disorders, Kansai Medical University, 570-8506 Osaka, cipient and transplanted thymuses in the IBM-BMT + TT setting. Japan; †JIMRO Co., Ltd., 370-0021 Gunma, Japan; and ‡Division of Clinical Pathol- Because we have found that TT using newborn thymus is most ogy, Toyooka Hospital, 668-8501 Hyogo, Japan effective in tumor suppression (18), we used newborn thymus in this Received for publication June 13, 2012. Accepted for publication January 3, 2013. study. We show in this article that CD4+ T cell–depleted lympho- 2 This work was supported by the Otsuka Pharmaceutical Company, Ltd., and by grants cyte infusion (CD4 -DLI) impairs neither the recovery of recipient from the Research on Allergic Disease and Immunology Committee from the Health thymus nor the development of transplanted thymus. and Labour Sciences Research of the Ministry of Health, Labour and Welfare. Address correspondence and reprint requests to Prof. Susumu Ikehara, Department of Stem Cell Disorders, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi Materials and Methods City, Osaka 570-8506, Japan. E-mail address: [email protected] Mice The online version of this article contains supplemental material. C57BL/6 (B6), enhanced GFP (eGFP) transgenic (tg) B6, and BALB/c mice Abbreviations used in this article: allo-BMT, allogeneic bone marrow transplantation; were purchased from Shimizu Laboratory Supplies (Shizuoka, Japan). B6, C57BL/6; BMC, bone marrow cell; BMT, bone marrow transplantation; DLI, Eight- to 12-wk-old male mice were used for BMT and DLI. For TT, donor lymphocyte infusion; eGFP, enhanced GFP; FasL, Fas ligand; GvHD, graft- 1 d after birth, B6 mice were sacrificed to obtain newborn thymuses. All the versus-host disease; IBM-BMT, intrabone marrow–BMT; tg, transgenic; Treg, regu- latory T cell; TT, thymus transplantation; WSP, whole spleen. mice were maintained in a specific pathogen-free room. This article is distributed under The American Association of Immunologists, Inc., Experimental protocol Reuse Terms and Conditions for Author Choice articles. As shown in Fig. 1, BALB/c mice were lethally irradiated with 7 Gy using Copyright Ó 2013 by The American Association of Immunologists, Inc. 0022-1767/13/$16.00 the Gammacell 40 Exactor (MDS Nordion, Kanata, ON, Canada) with two www.jimmunol.org/cgi/doi/10.4049/jimmunol.1201605 The Journal of Immunology 2977 [137Cs] sources, and the next day, these mice received IBM-BMT from B6 some mice were injected i.p. with 1 mg anti–TNF-a Ab and 2 mg anti-FasL mice (group I). Some mice additionally received TT from B6 mice (group Ab (WSP + Abs group) on days 0, 4, 8, and 12 as described previously (26). II). On the same day, some mice also received whole spleen (WSP-), CD42-, or CD82-DLI from B6 mice: WSP-DLI (group III), CD42-DLI Statistical analysis (group IV), and CD82-DLI (group V). The treated mice were sacrificed The results are represented as means 6 SD. The Student t test was used to 5 d, 2 wk, or 4 wk after the treatments. determine any statistical significance. A p value ,0.05 was considered to Reagents and flow cytometric analysis be a significant difference. The Abs used in this study were as follows: purified rat anti-mouse CD4 and CD8 Ab (eBioscience, San Diego, CA); FITC-conjugated anti-mouse Results CD4 and H-2Kb Ab; PE-conjugated anti-mouse H-2Kd, CD4, CD8, and In the IBM+TT setting, WSP-DLI induces serious GvHD but B220 Ab; and PerCP-Cy5.5–conjugated anti-mouse CD45 Ab (BD Phar- CD42 -DLI does not mingen, San Diego, CA). For the thymus and peripheral blood analysis, leukocytes were first gated by CD45+ cells, which were estimated as nu- We carried out IBM-BMT, TT, and DLI from B6 to BALB/c mice. clear cells. To analyze the percentage of regulatory T cells (Tregs) in the The protocol is described in detail in Fig. 1 and in Materials and spleen, we performed intracytoplasmic FoxP3 staining using an eBio- Methods. science FITC–anti-mouse/rat FoxP3 staining set in accordance with the manufacturer’s instructions. Samples were analyzed using an FACSCalibur The TT group (group II) showed similar results to group I (Fig. flow cytometer (BD Biosciences). 2), although TT provides an abundance of thymocytes (immature T cells), whereas DLI contains mature T cells and attacks the IBM-BMT and TT target organs after priming.
Load more

Recommended publications
  • Strokovno Poročilo UKCL 2019
    STROKOVNO POROČILO 2019 STROKOVNO POROČILO 2019 Univerzitetni klinični center Ljubljana, Zaloška cesta 2, 1000 Ljubljana Odgovorna oseba: prof. dr. Jadranka Buturović Ponikar, dr. med., strokovna direktorica UKC Ljubljana Besedila za poročilo so prispevali: prof. dr. Zlatko Fras, mag. Jana Brguljan Hitij, prof. dr. Aleš Blinc, prof. dr. Matjaž Šinkovec, prof. dr. Marko Noč, prof. dr. Marjeta Terčelj, prof. dr. Borut Štabuc, prof. dr. Miha Arnol, doc. dr. Andrej Janež, prof. dr. Samo Zver, prof. dr. Matija Tomšič, Gregor Veninšek, doc. dr. Miran Brvar, dr. Hugon Možina, prof. dr. Matjaž Veselko, dr. Nikola Lakić, prof. dr. Roman Bošnjak, prof. dr. Uroš Ahčan, prof. dr. Matej Cimerman, prof. dr. Aleš Tomažič, dr. Tomaž Štupnik, asist. Bojan Štrus, prof. dr. Andrej Kansky, prof. dr. Vesna Novak Jankovič, doc. dr. Igor Frangež, prof. dr. Simon Podnar, prof. dr. Uroš Rot, doc., prof. dr. Adolf Lukanovič, doc. dr. Borut Kobal, Mag. Gorazd Kavšek, prof. dr. Eda Vrtačnik Bokal, Leon Meglič, prof. dr. Borut Peterlin, doc.dr. Marko Pokorn, doc. dr. Anamarija Meglič, prim. Mojca Brecelj Kobe, prof. dr.Tadej Avčin, Uroš Krivec, prof. dr. Rok Orel, prof. dr. Tadej Battellino, prof. dr. Tanja Kersnik Levart, prof. dr. Janez Jazbec, prof. dr. Darja Paro Panjan, prof. dr. David Neubauer, mag. Mojca Tomažič, asist. dr. Veronika Velenšek, prof. dr. Milan Petelin, prof. dr. Martina Drevenšek, dr. Rok Kosem, doc.dr. Milan Kuhar, doc. dr. Tatjana Lejko Zupanc, prof. dr. Mojca Globočnik Petrović, prof. dr. Vane Antolič, doc. dr. Aleksandar Aničin, prim. asist. Tanja Planinšek Ručigaj, doc.dr.. Dimitrij Kuhelj, doc. dr. Katja Zaletel, prof. dr. Milan Skitek, prof.
    [Show full text]
  • Newsletteralumni News of the Newyork-Presbyterian Hospital/Columbia University Department of Surgery Volume 13, Number 1 Summer 2010
    NEWSLETTERAlumni News of the NewYork-Presbyterian Hospital/Columbia University Department of Surgery Volume 13, Number 1 Summer 2010 CUMC 2007-2009 Transplant Activity Profile* Activity Kidney Liver Heart Lung Pancreas Baseline list at year start 694 274 174 136 24 Deceased donor transplant 123 124 93 57 11 Living donor transplant 138 17 — 0 — Transplant rate from list 33% 50% 51% 57% 35% Mortality rate while on list 9% 9% 9% 15% 0% New listings 411 217 144 68 23 Wait list at year finish 735 305 204 53 36 2007-June 2008 Percent 1-Year Survival No % No % No % No % No % Adult grafts 610 91 279 86 169 84 123 89 6 100 Adult patients 517 96 262 88 159 84 116 91 5 100 Pediatric grafts 13 100 38 86 51 91 3 100 0 — Pediatric patients 11 100 34 97 47 90 2 100 0 — Summary Data Total 2009 living donor transplants 155 (89% Kidney) Total 2009 deceased donor transplants 408 (30% Kidney, 30% Liver) 2007-June 2008 adult 1-year patient survival range 84% Heart to 100% Pancreas 2007-June 2008 pediatric 1-year patient survival range 90% Heart to 100% Kidney or lung *Health Resource and Service Administration’s Scientific Registry of Transplant Recipients (SRTR) Ed Note. The figure shows the US waiting list for whole organs which will only be partially fulfilled by some 8,000 deceased donors, along with 6,600 living donors, who will provide 28,000 to 29,000 organs in 2010. The Medical Center’s role in this process is summarized in the table, and the articles that follow my note expand on this incredible short fall and its potential solutions.
    [Show full text]
  • Thymus Transplantation Reference Number: CP.MP.189 Coding Implications Date of Last Revision: 06/21 Revision Log
    Clinical Policy: Thymus Transplantation Reference Number: CP.MP.189 Coding Implications Date of Last Revision: 06/21 Revision Log See Important Reminder at the end of this policy for important regulatory and legal information. Description Complete DiGeorge anomaly is a disorder in which a person has no thymus function. Without thymus function, bone marrow stem cells do not develop into T cells, which results in immunodeficiency. Without successful treatment, patients usually die by 2 years of age. Thymus transplantation with and without immunosuppression has resulted in the development good T cell function in complete DiGeorge anomaly subjects.1 Policy/Criteria I. It is the policy of health plans affiliated with Centene Corporation® that thymus transplant (use of RVT-802) requires secondary review, due to limited evidence, when meeting all of the following: A. Complete or “atypical” DiGeorge syndrome with poor thymus function, per medical testing laboratory studies and physical examination, as confirmed by the thymus transplant clinical trial (NCT01220531); B. Immunodeficiency, or severe autoimmunity for which development of naïve T cells would be expected to lead to clinical improvement; C. Flow cytometry and phytohaemagglutinin (PHA) studies are planned to occur twice, once within 3 months of transplantation and once within one month of transplantation. Studies must be performed in a CLIA or CAP certified laboratory, preferably Duke Clinical Immunology Laboratory; D. None of the following contraindications: 1. Malignancy, except for non-melanoma localized skin cancer that has been treated appropriately, a malignancy that has been completely resected, or a treated malignancy determined to have a small likelihood of recurrence and acceptable future risks; 2.
    [Show full text]
  • Thymocytes May Persist and Differentiate Without Any Input from Bone Marrow Progenitors
    Brief Definitive Report Thymocytes may persist and differentiate without any input from bone marrow progenitors Laetitia Peaudecerf,1 Sara Lemos,1 Alessia Galgano,1 Gerald Krenn,1 Florence Vasseur,1 James P. Di Santo,2 Sophie Ezine,1 and Benedita Rocha1 1Institut National de la Santé et de la Recherche Médicale, Unit 1020, Faculty of Medicine Descartes Paris V, 75015 Paris, France 2Innate Immunity Unit, Pasteur Institute, 75724 Paris, France Thymus transplants can correct deficiencies of the thymus epithelium caused by the com- plete DiGeorge syndrome or FOXN1 mutations. However, thymus transplants were never used to correct T cell–intrinsic deficiencies because it is generally believed that thymocytes have short intrinsic lifespans. This notion is based on thymus transplantation experiments where it was shown that thymus-resident cells were rapidly replaced by progenitors origi- nating in the bone marrow. In contrast, here we show that neonatal thymi transplanted into interleukin 7 receptor–deficient hosts harbor populations with extensive capacity to self-renew, and maintain continuous thymocyte generation and export. These thymus transplants reconstitute the full diversity of peripheral T cell repertoires one month after surgery, which is the earliest time point studied. Moreover, transplantation experiments performed across major histocompatibility barriers show that allogeneic transplanted thymi are not rejected, and allogeneic cells do not induce graft-versus-host disease; transplants induced partial or total protection to infection. These results challenge the current dogma that thymocytes cannot self-renew, and indicate a potential use of neonatal thymus trans- plants to correct T cell–intrinsic deficiencies. Finally, as found with mature T cells, they show that thymocyte survival is determined by the competition between incoming progeni- tors and resident cells.
    [Show full text]
  • Results of Gal-Knockout Porcine Thymokidney Xenografts
    Results of Gal-Knockout Porcine Thymokidney Xenografts The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Griesemer, A. D., A. Hirakata, A. Shimizu, S. Moran, A. Tena, H. Iwaki, Y. Ishikawa, et al. 2009. “Results of Gal-Knockout Porcine Thymokidney Xenografts.” American Journal of Transplantation 9 (12) (December): 2669–2678. doi:10.1111/j.1600-6143.2009.02849.x. Published Version doi:10.1111/j.1600-6143.2009.02849.x Citable link https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37364476 Terms of Use This article was downloaded from Harvard University’s DASH repository, WARNING: This file should NOT have been available for downloading from Harvard University’s DASH repository.;This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/ urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA NIH Public Access Author Manuscript Am J Transplant. Author manuscript; available in PMC 2010 November 20. NIH-PA Author ManuscriptPublished NIH-PA Author Manuscript in final edited NIH-PA Author Manuscript form as: Am J Transplant. 2009 December ; 9(12): 2669±2678. doi:10.1111/j.1600-6143.2009.02849.x. Results of Gal-Knockout porcine thymokidney xenografts Adam D. Griesemer1, Atsushi Hirakata1, Akira Shimizu1, Shannon Moran1, Aseda Tena1, Hideyuki Iwaki1, Yoshinori Ishikawa1, Patrick Schule1, J. Scott Arn1, Simon C. Robson2, Jay A. Fishman3, Megan Sykes1, David H. Sachs1, and Kazuhiko Yamada1,4 1Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 2Transplant Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 3Division of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
    [Show full text]
  • Hematopoietic Stem Cell Transplantation for 30 Patients with Primary Immunodeficiency Diseases: 20 Years Experience of a Single Team
    Bone Marrow Transplantation (2006) 37, 469–477 & 2006 Nature Publishing Group All rights reserved 0268-3369/06 $30.00 www.nature.com/bmt ORIGINAL ARTICLE Hematopoietic stem cell transplantation for 30 patients with primary immunodeficiency diseases: 20 years experience of a single team Y Tsuji1, K Imai1,2, M Kajiwara1,3, Y Aoki1, T Isoda1, D Tomizawa1, M Imai1, S Ito1, H Maeda1, Y Minegishi1, H Ohkawa1, JYata 1, N Sasaki4, K Kogawa2, M Nagasawa1, T Morio1, S Nonoyama2 and S Mizutani1 1Department of Pediatrics and Developmental Biology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan; 2Department of Pediatrics, National Defense Medical College, Saitama, Japan; 3Department of Blood Transfusion, University Hospital Faculty of Medicine, Tokyo Medical and Dental University, Tokyo, Japan and 4Department of Pediatrics, Saitama Medical School, Saitama, Japan We retrospectively analyzed our results of 30 patients with Introduction three distinctive primary immunodeficiency diseases (PIDs) – severe combined immunodeficiency (SCID, n ¼ 11), Primary immunodeficiency diseases (PIDs) are often Wiskott–Aldrich syndrome (WAS, n ¼ 11) and X-linked accompanied with life-threatening infections. Hematopoie- hyper-immunoglobulin M (IgM) syndrome (XHIM, n ¼ 8) tic SCT (HSCT) can be a treatment of choice to cure most – who underwent hematopoietic SCT (HSCT) during the of the lethal forms of immunodeficiencies, including severe past 20 years. Until 1995, all donors were HLA- combined immunodeficiency (SCID), Wiskott–Aldrich haploidentical relatives with T-cell depletion (TCD) syndrome (WAS) and X-linked hyper immunoglobulin M (n ¼ 8). Since 1996, the donors have been HLA-matched (IgM) syndrome (XHIM). An HLA-matched related donor related donors (MRD) (n ¼ 8), unrelated BM (UR-BM) (MRD), the best hematopoietic stem cell source, may not (n ¼ 7) and unrelated cord blood (UR-CB) (n ¼ 7).
    [Show full text]
  • Selected Abstracts from the 12 Annual
    Journal of Clinical Immunology (2021) 41 (Suppl 1):S1–S135 https://doi.org/10.1007/s10875-021-01001-x ABSTRACTS Selected Abstracts from the 12th Annual Meeting of the Clinical Immunology Society: 2021 Virtual Annual Meeting: Immune Deficiency and Dysregulation North American Conference Published online: 6 April 2021 # Springer Science+Business Media, LLC, part of Springer Nature 2021 Virtual, April 14-17 The study samples were cleared cryo-poor plasma. A chromatographic process using a new cation-exchange (CEX) resin that binds with high Sponsorship: Publication of this supplement was funded by the capacity to IgG and removes procoagulant activities was added in a se- Clinical Immunology Society. All content was reviewed and approved quential step to the standard removal/inactivation process. Testing of the by the Program Committee, which held full responsibility for the samples was performed using the standard process alone and then with abstract selections. sequential addition of the new CEX process. Procoagulant activity was tested using several standard methods, including, thrombin generation All contributors have provided original material assay, chromogenic FXIa assay, non-activated partial thromboplastin as submitted for publication in the Journal time (NaPTT), and FXI/FXIa ELISA. We further spiked our samples with of Clinical Immunology. additional coagulation factor XIa, in amounts exceeding any variability that may be caused due to sample differences, and tested these samples 01 Oral Presentations for procoagulant activity using the same methods. The procoagulant activities were reduced to low levels as determined by the thrombin generation assay: < 1.56 mIU/mL, chromogenic FXIa assay: < 0.16 mIU/mL, NaPTT: >250 s, FXI/FXIa ELISA: < 0.31 ng/mL.
    [Show full text]
  • T-Cell Reconstitution After Thymus Xenotransplantation Induces Hair Depigmentation and Loss Anna L
    ORIGINAL ARTICLE T-Cell Reconstitution after Thymus Xenotransplantation Induces Hair Depigmentation and Loss Anna L. Furmanski1, Ryan F.L. O’Shaughnessy1, Jose Ignacio Saldana1, Michael P. Blundell2, Adrian J. Thrasher2,NeilJ.Sebire3,E.GrahamDavies2,4 and Tessa Crompton1 Here we present a mouse model for T-cell targeting of hair follicles, linking the pathogenesis of alopecia to that of depigmentation disorders. Clinically, thymus transplantation has been successfully used to treat T-cell immunodeficiency in congenital athymia, but is associated with autoimmunity. We established a mouse model of thymus transplantation by subcutaneously implanting human thymus tissue into athymic C57BL/6 nude mice. These xenografts supported mouse T-cell development. Surprisingly, we did not detect multiorgan autoimmune disease. However, in all transplanted mice, we noted a striking depigmentation and loss of hair follicles. Transfer of T cells from transplanted nudes to syngeneic black-coated RAG À / À recipients caused progressive, persistent coat-hair whitening, which preceded patchy hair loss in depigmented areas. Further transfer experiments revealed that these phenomena could be induced by CD4 þ T cells alone. Immunofluorescent analysis suggested that Trp2 þ melanocyte-lineage cells were decreased in depigmented hair follicles, and pathogenic T cells upregulated activation markers when exposed to C57BL/6 melanocytes in vitro, suggesting that these T cells are not tolerant to self-melanocyte antigens. Our data raise interesting questions about the mechanisms underlying tissue-specific tolerance to skin antigens. Journal of Investigative Dermatology (2013) 133, 1221–1230; doi:10.1038/jid.2012.492; published online 10 January 2013 INTRODUCTION et al., 2007). Autoimmune vitiligo in humans typically Alopecia is a disfiguring form of hair loss, which may be presents as patchy skin depigmentation resulting from a reversible, or irreversible, as in scarring alopecias.
    [Show full text]
  • Division of Immunogenetics Division of Immunogenetics
    DIVISION OF IMMUNOGENETICS diVision of ImmunoGenetics Mission The Division of Immunogenetics is committed to providing basic science support aimed at better understanding the etio-pathogenesis of pediatric diseases to more efficiently and correctly diagnose, prevent, and possibly 136 better treat them. 137 DEPARTMENT OF PEDIATRICS 2012 ANNUAL REPORT DEPARTMENT OF PEDIATRICS 2012 ANNUAL REPORT DIVISION OF IMMUNOGENETICS DIVISION OF IMMUNOGENETICS facultY AND staff To block auto-immunity, without the use of immunosuppressant, Nick Giannoukakis and Massimo Trucco have success- fully completed a National Institutes of Health (NIH)-funded, U.S. Food and Drug Administration (FDA)-approved Massimo Trucco, MD Yong Fan, PhD Steven Ringquist, PhD phase I clinical trial that was designed to test the safety of a treatment in which autologous DC—rendered functionally Hillman Professor of Research Assistant Professor Research Assistant Professor immature by exposing them to CD40, CD80, and CD86 antisense oligodeoxyribonucleotides (AS-ODN) to reduce Pediatric Immunology costimulatory molecule levels at their surface—were administered to T1D patients with established disease. Leukocytes Nick Giannoukakis, PhD William Rudert, MD, PhD of the patient were obtained by apheresis, and DCs were then isolated and expanded. DC engineered in GMP facilities Suzanne Bertera, PhD Associate Professor Research Associate Professor to express low levels of CD40, CD80, and CD86 were then injected into the patient by intradermal administration at an Research Assistant Professor Jing He, MD, PhD Tatyana Votyakova, MD, PhD anatomical site proximal to the pancreas. DCs then migrate to the nearest (i.e., pancreatic) lymph nodes, where they are Rita Bottino, PhD Research Assistant Professor Research Assistant Professor able to interrupt the vicious circle that maintains islet-specific inflammation (i.e., insulitis).
    [Show full text]
  • Memory-Enriched Population Aged Microenvironment Results in a Lymphocytes in the + Maturation Of
    Maturation of CD4+ Lymphocytes in the Aged Microenvironment Results in a Memory-Enriched Population This information is current as Jenna A. Timm and Marilyn L. Thoman of September 25, 2021. J Immunol 1999; 162:711-717; ; http://www.jimmunol.org/content/162/2/711 Downloaded from References This article cites 44 articles, 19 of which you can access for free at: http://www.jimmunol.org/content/162/2/711.full#ref-list-1 Why The JI? Submit online. http://www.jimmunol.org/ • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average by guest on September 25, 2021 Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 1999 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Maturation of CD41 Lymphocytes in the Aged Microenvironment Results in a Memory-Enriched Population1 Jenna A. Timm and Marilyn L. Thoman2 With advancing age the CD41 T lymphocyte compartment becomes enriched for memory cells in both humans and experimental animals. Although it has been assumed that the shift from a naive to a memory-dominant population is due to a lifetime of antigenic exposure and selection as well as a loss of naive cell input due to reduced thymopoiesis, the present data suggest that the aged microenvironment influences the maturation of newly produced CD41 T cells.
    [Show full text]
  • FINAL PROGRAM DAY 1 - August 18 DAY 2 - August 19 DAY 3 - August 20
    FINAL PROGRAM DAY 1 - August 18 DAY 2 - August 19 DAY 3 - August 20 Registration (all day) Registration (all day) Registration (all day) Early Morning Symposia 07:00–08:15 Post- Pre- Post-Graduate Plenary Session 1: Graduate Congress Courses Basic and Translational Courses Meeting 08:30–13:00 Sciences 08:30–13:00 14:00–17:30 14:00–17:30 TID 2016 08:30–10:00 Conference 08:30–18:00 Co"ee Break 10:00–10:30 Orals and Mini-Orals Sessions 10:30–12:30 Lunch Break / Industry Exhibition Symposium Exhibition Set-up Exhibition Set-up 12:30–13:30 12:30–13:30 State-of-the-Art Sessions Exhibition 13:30–15:00 Co"ee Break 15:00–15:30 Orals Sessions 15:30–17:00 WIT Camp!re Wkshop and & Net. Poster Event Sessions Opening Ceremony Industry 17:00– 17:00– 17:30–18:30 Symp. 19:00 18:30 17:30– 19:00 Welcome Reception 18:30–20:00 Exhibition Young Investigators’ Networking Event 19:30–21:30 (ticketed) DAY 4 - August 21 DAY 5 - August 22 DAY 6 - August 23 Registration (all day) Registration (all day) Registration (all day) Early Morning Symposia Early Morning Symposia Early Morning Symposia 07:00–08:15 07:00–08:15 07:00–08:15 Plenary Session 2: Plenary Session 3: Plenary Session 4: Antibody Mediated Injury Hepatitis C Virus in Transformational Sciences Solid Organ Transplantation: in Transplantation? Have the Rules Changed? 08:30–10:00 08:30–10:00 08:30–10:00 Co!ee Break Co!ee Break Co!ee Break 10:00–10:30 10:00–10:30 10:00–10:30 Orals and Mini-Orals President’s Plenary Orals Sessions and Awards Sessions 10:30–12:30 10:30–12:30 10:30–12:00 Plenary Session 5: What
    [Show full text]
  • Thymic Rejuvenation and the Induction of Tolerance by Adult Thymic Grafts
    Thymic rejuvenation and the induction of tolerance by adult thymic grafts Shuji Nobori, Akira Shimizu, Masayoshi Okumi, Emma Samelson-Jones, Adam Griesemer, Atsushi Hirakata, David H. Sachs, and Kazuhiko Yamada* Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02129 Edited by Ralph M. Steinman, The Rockefeller University, New York, NY, and approved October 25, 2006 (received for review June 22, 2006) The thymus, the site of origin of T cell immunity, shapes the repertoire procedure and then facilitated the induction of tolerance, suggest- of T cell reactivity through positive selection of developing T cells and ing that thymic function is largely controlled by the host environ- prevents autoimmunity through negative selection of autoreactive T ment rather than by the local thymic milieu. cells. Previous studies have demonstrated an important role for the thymus not only in central deletional tolerance, but also in the Results induction of peripheral tolerance by vascularized renal allografts in Thymic Involution with Age In Miniature Swine. We first examined juvenile miniature swine recipients. The same protocol did not induce the natural course of thymic involution with aging in naive minia- tolerance in thymectomized recipients nor in recipients beyond the ture swine (9). Right cervical thymic lobes were biopsied from 53 age of thymic involution. We subsequently reported that vascularized naive Massachusetts General Hospital (MGH) miniature swine of thymic lobe grafts from juvenile donors were capable of inducing different ages. The cortex and medulla in whole biopsy specimens tolerance in thymectomized juvenile hosts. However, the important containing at least 10 lobules were subjected to morphometric question remained whether aged, involuted thymus could also in- analysis by using NIH Image (Scion Image) software (10).
    [Show full text]