DOCSLIB.ORG

Cells Involved in Cell-Mediated and Transplantation Immunity in the Rabbit, I

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Cells Involved in Cell-Mediated and Transplantation Immunity in the Rabbit, I Proceedings of the National Academy of Sciences Vol. 65, No. 1, pp. 70-73, January 1970 Cells Involved in Cell-Mediated and Transplantation Immunity in the Rabbit, I. The Noninvolvement of the Bone Marrow Antigen Reactive Cell in the Transplant Rejection Reaction* Maxwell Richter,t Nabih I. Abdou, and Robert D. Midgley THE HARRY WEBSTER THORP LABORATORIES, DIVISION OF IMMUNOCHEMISTRY AND ALLERGY, AND THE DEPARTMENT OF SURGERY, ROYAL VICTORIA HOSPITAL, MONTREAL, QUEBEC, CANADA Communicated by Wilder Penfield, October 28, 1969 Abstract. Rabbits were subjected to 800 r total body irradiation to render them immunoincompetent with respect to the humoral immune response. These rabbits were, however, only slightly less capable of rejecting skin allografts than nonirradiated rabbits. Furthermore, the administration of normal or specifi- cally "primed" bone marrow cells (bone marrow obtained from a rabbit injected one to two days previously with the spleen cells obtained from the prospective skin donor) did not enhance or inhibit the graft rejection reaction. It is con- cluded that the cells mediating the humoral immune response are different from those mediating the cellular immune response. Introduction. Previous investigations from this laboratory have established that at least two cell-types are required for the mediation of the humoral immune response in the rabbit, the antigen-reactive cell and the antibody-forming cell.'-3 The antigen-reactive cell has been localized to the bone marrow.4 By subjecting normal rabbits to varying doses of irradiation, coupled with cell transfer experi- ments, we have previously demonstrated that a dependent relationship exists between the capacity of the rabbit to synthesize humoral antibody and the presence of functionally active antigen-reactive cells in the bone marrow.5 Evidence has also been presented strongly suggesting that these cells vacate the bone marrow after contact with the antigen, leaving behind antigen-reactive cells capable of transferring immunocompetence to a recipient 800 r irradiated rabbit with respect to all antigens except the one used to immunize the cell donor." 2 Since the bone marrow can be depleted of antigen-reactive cells pre- committed to interact with an antigen as complex as the lymphocyte,7 it was proposed to utilize the cell transfer system to determine the role of antigen- reactive cells in transplant rejection reactions. As will be seen below, the bone marrow antigen-reactive cell does not play a role in the mediation of this reaction. Materials and Methods. Black outbred rabbits were selected as both the spleen cell and skin donors and New Zealand white rabbits were used as the bone marrow donors and as the irradiated bone marrow recipients (Fig. 1). The spleen was excised from a rabbit intravenously anesthetized with nembutal (30 mg/kg body weight). The spleen 70 Downloaded by guest on September 26, 2021 VOL. 65, 1970 MICROBIOLOGY: RICHTER ET AL. 71 NORMAL BLACK RABBIT NORMAL WHITE RABBIT (donor B-I)7 (donor W-I) CELLS /,- (5x 10) z / SKIN PRIMED (day 1) ALLOGRAFT BONE MARROW CELLS (5x 108) TIME (in days) FOR REJECTION OF SKIN ALLOGRAFT FROM DONOR B-I FIG. 1.-Protocol for the demonstration of different cell pathways resulting in humoral immunity and transplant rejection. cell suspension was prepared by application of slight pressure on spleen fragments through a wire mesh (50 mesh) into Medium 199 (Med 199) (Microbiological Assoc., Bethesda, Md.). The spleen cells were centrifuged and resuspended in Med 199 to a cell concen- tration of 108 splenic lymphoid cells per milliliter. The spleen cells (5 X 108) were then intravenously injected into a normal white rabbit. Twenty-four or 48 hr later, the rabbit was sacrificed and bone-marrow cell suspensions (referred to as primed bone marrow) were prepared as previously described." 2 These bone-marrow cells were then injected into 800 r irradiated white rabbits which served as the skin graft recipients. Skin grafts were performed as follows: Under intravenous nembutal anesthesia, the backs of both donor and recipient rabbits were shaved and prepped with Tincture of Merthiolate, using sterile technique with appropriate draping. The full thickness donor skin was removed, defatted, and placed on sterile saline-soaked gauzes. The donor site was closed primarily with 4-0 nylon sutures. A full thickness defect 2 cm in diameter was created on the backs of recipient rabbits and, using sterile technique, the donor skin was tailored to fit the recipient bed and held in place by means of interrupted 4-0 nylon sutures with a tie-over bolus dressing. The entire area was immobilized by means of collodion preparation of the surrounding nonoperated area and circumferential Kling dressing. The rabbits were placed in single cages. The dressings were removed and changed at 5- to 7-day intervals to allow for observation of take or rejection of the skin graft. The criteria for rejection of the skin grafts were those described by Billingham.6 The recipients of bone marrow primed with allogeneic splenic lymphocytes were bled at intervals of time and tested for the presence of circulating cytotoxic antibodies directed to leukocytes of the lymphocyte donor. The procedures used to detect these antibodies have been presented in detail previously.7 Results. As can be seen in Table 1, irradiated (800 r) rabbits were capable of rejecting skin allografts to the same extent as nonirradiated control rabbits. The transfer of normal or "primed" allogeneic bone marrow cells to irradiated Downloaded by guest on September 26, 2021 72 MICROBIOLOGY: RICHTER ET AL. PROC. N. A. S. rabbits did not interfere with or enhance their capacity to reject the skin grafts. On the other hand (not shown in Table 1), irradiated recipients of normal bone marrow cells could mount an immune response directed toward lymphocytes of the skin graft donor (cytotoxic titers of 30 to 100), whereas irradiated recipients of primed bone marrow (primed with respect to lymphoid cells of the skin donor) were unable to form detectable quantities of circulating antibodies toward the cells of the skin donor. TABLE 1. The rejection of skin allografts by irradiated (800r) rabbits given either normal or primed allogeneic bone marrow cells. Irradiated white recipient rabbit injected with primed* bone marrow cells obtained Skin allograft Time (in days) from donor injected with obtained from for rejection spleen cells obtained from following of skin following black rabbit black rabbit allograft B 1 16-18 B I B 1 15-17 B 1 B 2 14-16 B 1 B 3 16-18 B 2 18-21 B 2 B 1 17-19 B 2 B 2 15-18 B 2 B 3 14-17 Recipient irradiated only B 1 19-21 (no marrow cells transferred) B 2 16-19 B 3 15-19 Control, non-irradiated rabbit B 1 15-17 (no cells transferred) B 2 14-17 B 3 14-18 * Primed bone marrow is that obtained from a rabbit 1 to 2 days following immunization with the antigen. Discussion. Previous investigations conducted in this laboratory have unequivocally implicated an interaction between two cell types in the successful mediation of the humoral immune response-the bone marrow antigen-reactive cell (ARC) and the antibody-forming cell (AFC) of as yet undetermined origin.3 The ARC cell has been shown to be relatively radio-sensitive to 800 r in vivo irradiation2' 3 since the bone marrow cells of such a rabbit cannot transfer anti- body-forming capacity to other 800 r irradiated rabbits. The recovery of the capacity of the irradiated rabbit to synthesize humoral antibodies parallels the recovery of the ARC cells in the bone marrow,5 with complete recovery by 4 to 6 weeks. Bone-marrow cells obtained from rabbits one to two days following immunization with an antigen, i.e., sheep red blood cells (S-rbc), could not transfer immunocompetence to 800 r irradiated rabbits with respect to S-rbc whereas they could transfer immunocompetence with respect to all other antigens.2 These data suggest that the ARC cells vacate the bone marrow after contact with the antigen in vivo, leaving behind a bone marrow deficient in ARC cells directed toward the immunizing antigen. These findings were consistently obtained regardless of whether the antigen used was an inanimate protein,2 a nonreplicating red blood cell,2 or a viable, potentially proliferative lymphocyte.' On the basis of these findings, a protocol was devised to deter- Downloaded by guest on September 26, 2021 VOL. 65, 1970 MICROBIOLOGY: RICHTER ET AL. 73 mine the role of the ARC cell in the induction of cellular-type immunity, as represented by the transplant rejection reaction. If the ARC cell does have a specific function here, then the irradiated recipients of lymphocyte-primed bone marrow should not be able to reject skin transplants obtained from the rabbit which had originally donated lymphocytes used to prime the bone marrow donor until their own ARC cell had regenerated. Such was not the case, how- ever. The irradiated recipients of primed bone marrow cells were able to reject skin grafts as effectively as irradiated rabbits not given any bone marrow cells or given normal allogeneic bone marrow cells. It would therefore appear that the capacity to reject an allogeneic transplant does not involve the mediation of the ARC cell. Whether the capacity to evoke cellular immunity is entirely defined by a unique type of immunocompetent cell or by the antibody-forming cell identical to that mediating humoral immunity remains to be determined. However, if the latter is the case, then it would appear that the same cell capable of mediating cellular immunity (efferent limb of immune response) would also possess the capacity to "recognize" and interact with the original antigen (afferent limb of immune response), a property possessed by the memory cell mediating humoral immunity but not by the virgin ARC or AFC cell in the rabbit,2' 3 mouse, and rat.8-10 Experiments are currently in progress to better define the relationship of the cells mediating the humoral and cellular immune responses in the rabbit.
Load more

Recommended publications
  • Transplant Immunology.Pdf
    POLICY BRIEFING Transplant Immunology September 2017 The British Society of Immunology is the largest Introduction immunology society in Europe. Our mission is to promote excellence in immunological research, scholarship and Transplantation is the process of moving cells, tissues, or clinical practice in order to improve human and animal organs, from one site to another, either within the same health. We represent the interests of more than 3,000 person or between a donor and a recipient. If an organ immunologists working in academia, clinical medicine, system fails, or becomes damaged as a consequence of and industry. We have strong international links and disease or injury, it can be replaced with a healthy organ collaborate with our European, American and Asian or tissue from a donor. partner societies in order to achieve our aims. Organ transplantation is a major operation and is only Key points: offered when all other treatment options have failed. Consequently, it is often a life-saving intervention. In • Transplantation is the process of moving cells, 2015/16, 4,601 patient lives were saved or improved in i tissues or organs from one site to another for the the UK by an organ transplant. Kidney transplants are purpose of replacing or repairing damaged or the most common organ transplanted on the NHS in diseased organs and tissues. It saves thousands the UK (3,265 in 2015/16), followed by the liver (925), and i of lives each year. However, the immune system pancreas (230). In addition, a total of 383 combined heart poses a significant barrier to successful organ and lung transplants were performed, while in 2015/16.
    [Show full text]
  • 9. Types of Rejection Table of Contents 9.1 Antibody-Mediated Rejection
    9. Types of rejection Table of Contents 9.1 Antibody-mediated rejection 9.2 Chronic rejection 9.3 Hyperacute rejection 9.4 T-cell mediated rejection 9.5 Donor specific cell free DNA marker 9.1 Antibody-mediated rejection The 2019 Expert Consensus from the Transplantation Society Working Group (2020). Recommended Treatment for Antibody-mediated Rejection after Kidney Transplantation. Transplantation. 2020 Jan 8. doi: 10.1097/TP.0000000000003095. [Epub ahead of print]. Retrieved from: https://www.ncbi.nlm.nih.gov/pubmed/31895348 • A consensus of expert opinion in regards to standard of care treatment for active and chronic active AMR after kidney transplantation Yamanashi K, Chen-Yoshikawa TF, Hamaji M, et al (2020). Outcomes of combination therapy including rituximab for antibody-mediated rejection after lung transplantation. Gen Thorac Cardiovasc Surg. 2020;68(2):142–149. doi:10.1007/s11748-019-01189-1. Retrieved from: https://europepmc.org/article/med/31435872 • This study is a retrospective analysis of a single center’s experience of using combination therapy (methylprednisolone, plasma exchange, and IVIG) including rituximab for post lung transplant AMR in Japanese patients. Spica D, Junker T, Dickenmann M, et al (2019). Daratumumab for Treatment of Antibody-Mediated Rejection after ABO-Incompatible Kidney Transplantation. Case Rep Nephrol Dial. 2019;9(3):149–157. Published 2019 Nov 13. doi:10.1159/000503951. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902247/ • A case report detailing the use of Daratnumumab for treatment of therapy-refractory AMR in the context of ABO-incompatible kidney transplantation. Kincaide E, Hitchman K, Hall R, Yamaguchi I, Ding Y, Crowther B (2019).
    [Show full text]
  • Chronic Rejection Autoimmunity
    Antibodies to MHC Class I Induce Autoimmunity: Role in the Pathogenesis of Chronic Rejection This information is current as Naohiko Fukami, Sabarinathan Ramachandran, Deepti Saini, of September 26, 2021. Michael Walter, William Chapman, G. Alexander Patterson and Thalachallour Mohanakumar J Immunol 2009; 182:309-318; ; doi: 10.4049/jimmunol.182.1.309 http://www.jimmunol.org/content/182/1/309 Downloaded from References This article cites 54 articles, 10 of which you can access for free at: http://www.jimmunol.org/content/182/1/309.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • 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 by guest on September 26, 2021 *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 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 © 2009 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Antibodies to MHC Class I Induce Autoimmunity: Role in the Pathogenesis of Chronic Rejection1 Naohiko Fukami,* Sabarinathan Ramachandran,* Deepti Saini,* Michael Walter,‡ William Chapman,* G. Alexander Patterson,§ and Thalachallour Mohanakumar2*† Alloimmunity to mismatched donor HLA-Ags and autoimmunity to self-Ags have been hypothesized to play an important role in immunopathogenesis of chronic rejection of transplanted organs.
    [Show full text]
  • Hypersensitivity Reactions Corenotes by Core Concepts Anesthesia Review, LLC
    Hypersensitivity Reactions CoreNotes by Core Concepts Anesthesia Review, LLC 1. There are 4 types of hypersensitivity reactions. 2. Type 1 reactions are immediate-type reactions, including anaphylaxis. Signs & symptoms are the result of the release of histamine and other autocoids from mast cells & basophils. 3. Type 2 reactions are cytotoxic reactions and are cell mediated. ABO- incompatibility reactions are of this type. 4. Type 3 reactions are the result of soluble antigens and antibodies combining to form insoluble complexes. Neutrophils are activated and tissue damage results. Serum sickness and Arthus reactions are examples of Type 3 reactions 5. Type 4 reactions are also known as delayed hypersensitivity reactions. These are the result of antigens reacting with sensitized lymphocytes. Contact dermatitis is an example of a Type 4 reaction Type 1 hypersensitivity reactions involve the combination of antigen with circulating IgE. This produces degranulation of basophils and mast cells with the release of histamine and other autocoids. Type 1 reactions require previous exposure to the antigen, thereby causing the production of the IgE. Type 2 hypersensitivity reactions are antibody dependent, cell-mediated reactions. These reactions are mediated through IgG or IgM antibodies directed against cellular surface antigens. Previous exposure, as in ABO-incompatibility reactions, is not required. Cell damage from type 2 reactions is the result of cell lysis with complement activation and subsequent phagocytosis. Type 3 hypersensitivity reactions are also known as immune-complex reactions. These reactions result from soluble antigens and antibodies combining to form insoluble complexes, which deposit in the microvasculature. The subsequent inflammatory process then produces tissue damage.
    [Show full text]
  • AUTOIMMUNITY Transplant Rejection AIDS
    AUTOIMMUNITY Transplant rejection AIDS P. Babál ÚPA LFUK AUTOIMMUNITY Allergy - reaction to an allergen from the environment Autoimmunity- immune mechanisms oriented against components of self tissues Ehrlich: “horror autotoxicus” - reparative processes - frequently accompanied by antibodies against altered tissues (faster removal of these tissues) - if autoantibodies persist permanently -> autoimmunity - organ specific - systemic MECHANISMS BY WHICH AUTOIMMUNITY DEVELOPS Release of sequestered Ag - spermatozoa, lens, myelin Abnormal T-cell function: - Systemic lupus erythematodes, diminished Ts function other AI diseases Enhanced Th cell function - hemolytic anemias Polyclonal B cell activation - SLE, EBV-induced anti-DNA Ab GENETIC FACTORS in autoimmunity HLA system of genes - regulates immune responses = individuals with certain HLA genes expression are at higher risk to develop AI disease Ankylotic spondyllitis B27 87.4 % Autoimmune thyreotoxicosis DR3 3.7 Hashimoto thyroiditis DR5 3.2 Diabetes mellitus II. DR3 3.3 Sclerosis multiplex DR2 4.1 Goodpasture sy. DR2 15.9 Autoimmune diseases of NERVE SYSTEM Systemic polyradiculoneuropathy (Guillain-Barre sy.) - 3/4 weeks after viral infection = demyelinization of motor neurons … anti-myelin Ab Myastenia gravis autoAb reacting with receptors for ACH at the neuro-muscular disc (block, destruction) -> weakness. Result of Ts failure to suppress autoimmune B-cell clones Acute allergic encephalomyelitis - 2 weeks after viral infection, usually measles (morbilli) typical perivascular demyelinization
    [Show full text]
  • B Cell Immunity in Solid Organ Transplantation
    REVIEW published: 10 January 2017 doi: 10.3389/fimmu.2016.00686 B Cell Immunity in Solid Organ Transplantation Gonca E. Karahan, Frans H. J. Claas and Sebastiaan Heidt* Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands The contribution of B cells to alloimmune responses is gradually being understood in more detail. We now know that B cells can perpetuate alloimmune responses in multiple ways: (i) differentiation into antibody-producing plasma cells; (ii) sustaining long-term humoral immune memory; (iii) serving as antigen-presenting cells; (iv) organizing the formation of tertiary lymphoid organs; and (v) secreting pro- as well as anti-inflammatory cytokines. The cross-talk between B cells and T cells in the course of immune responses forms the basis of these diverse functions. In the setting of organ transplantation, focus has gradually shifted from T cells to B cells, with an increased notion that B cells are more than mere precursors of antibody-producing plasma cells. In this review, we discuss the various roles of B cells in the generation of alloimmune responses beyond antibody production, as well as possibilities to specifically interfere with B cell activation. Keywords: HLA, donor-specific antibodies, antigen presentation, cognate T–B interactions, memory B cells, rejection Edited by: Narinder K. Mehra, INTRODUCTION All India Institute of Medical Sciences, India In the setting of organ transplantation, B cells are primarily known for their ability to differentiate Reviewed by: into long-lived plasma cells producing high affinity, class-switched alloantibodies. The detrimental Anat R. Tambur, role of pre-existing donor-reactive antibodies at time of transplantation was already described in Northwestern University, USA the 60s of the previous century in the form of hyperacute rejection (1).
    [Show full text]
  • Immune Globulins (Immunoglobulin): Asceniv; Bivigam; Carimune NF
    Immune Globulins (immunoglobulin): Asceniv; Bivigam; Carimune NF; Flebogamma; Gamunex-C; Gammagard Liquid; Gammagard S/D; Gammaked; Gammaplex; Octagam; Privigen; Panzyga (Intravenous) Document Number: IC-0071 Last Review Date: 10/01/2020 Date of Origin: 07/20/2010 Dates Reviewed: 09/2010, 12/2010, 02/2011, 03/2011, 06/2011, 09/2011, 10/2011, 12/2011, 03/2012, 06/2012, 09/2012, 12/2012, 03/2013, 05/2013, 06/2013, 09/2013, 12/2013, 03/2014, 06/2014, 09/2014, 12/2014, 03/2015, 06/2015, 09/2015, 12/2015, 03/2016, 06/2016, 09/2016, 12/2016, 03/2017, 06/2017, 09/2017, 12/2017, 03/2018, 06/2018, 09/2018, 10/2018, 05/2019, 10/2019, 10/2020 I. Length of Authorization Initial and renewal authorization periods vary by specific covered indication. Unless otherwise specified, the initial authorization will be provided for 6 months and may be renewed annually. II. Dosing Limits A. Quantity Limit (max daily dose) [NDC unit]: # of vials Drug Vial size in IgG grams One time only per 28 days LOAD MAINTENANCE Asceniv 5 18 18 5 1 1 Bivigam 10 23 23 3,6 1 1 Carimune NF 12 19 19 5, 10, 20 1 1 Flebogamma 10% DIF 20 11 11 2.5, 5, 10 1 1 Flebogamma 5% DIF 20 11 11 1, 2.5, 5, 10, 20 1 1 Gamunex-C 40 6 6 1, 2.5, 5, 10, 20 1 1 Gammagard Liquid 30 8 8 Proprietary & Confidential © 2020 Magellan Health, Inc. 5 1 1 Gammagard S/D 10 23 23 1, 2.5, 5, 10 1 1 Gammaked 20 11 11 2.5, 5, 10 1 1 Gammaplex 20 11 11 2, 5, 10 1 1 Octagam 10% 20 11 11 1, 2.5, 5, 10 1 1 Octagam 5% 25 9 9 5, 10, 20 1 1 Privigen 40 6 6 Panzyga 1, 2.5, 5, 10, 20 1 1 30 8 8 B.
    [Show full text]
  • "Graft Rejection: Immunological Suppression"
    Graft Rejection: Advanced article Immunological Article Contents . Introduction Suppression . Role of Tissue Typing . Immunosuppressive Agents . Reducing Immunogenicity of Grafts Behdad Afzali, King’s College London, London, UK . Induction of Transplantation Tolerance Robert Lechler, King’s College London, London, UK Online posting date: 15th September 2010 Giovanna Lombardi, King’s College London, London, UK Based in part on the previous version of this Encyclopedia of Life Sciences (ELS) article, ‘‘Graft Rejection: Immunological Suppression’’ by ‘‘Kathryn J Wood.’’ Transplantation of solid organs is the treatment of choice immune system. Transplantation of cells, tissues or an for most patients with end-stage organ diseases. In the organ between genetically nonidentical individuals (allo- absence of pharmacological immunosuppression, recog- geneic) in the same species or between different species nition of foreign (allogeneic) histocompatibility proteins (xenogeneic) leads to activation of the recipient’s immune expressed on donor cells by the recipient’s immune system system and an immunological reaction against the trans- plant. In this setting, the transplanted tissue(s) (referred to results in rejection of the transplanted tissue(s). One-year as the ‘graft’ – Table 1) is destroyed (rejected) if no further renal transplant survival is now routinely over 90% in intervention is taken. See also: Transplantation most centres, largely the result of improvements in Studies on the behaviour of tumour grafts by Little and immunosuppressive drugs. In this article, we review Tyzzer, among others, led Gorer to propose the concept of commonly used immunosuppressive medications and graft rejection as long ago as 1938. Recognition that the discuss their pharmacological modes of action. Given that immune system was responsible came later when Gibson long-term graft outcomes remain poor despite improve- and Medawar clearly identified specificity and memory as ments in early transplant survival, we discuss, in addition, hallmark features of the rejection response.
    [Show full text]
  • Donor-Derived Cell-Free DNA in Kidney Transplantation As a Potential Rejection Biomarker: a Systematic Literature Review
    Journal of Clinical Medicine Review Donor-Derived Cell-Free DNA in Kidney Transplantation as a Potential Rejection Biomarker: A Systematic Literature Review Adrian Martuszewski 1 , Patrycja Paluszkiewicz 1 , Magdalena Król 2, Mirosław Banasik 1 and Marta Kepinska 3,* 1 Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland; [email protected] (A.M.); [email protected] (P.P.); [email protected] (M.B.) 2 Students Scientific Association, Department of Biomedical and Environmental Analysis, Faculty of Pharmacy, Wroclaw Medical University, 50-556 Wroclaw, Poland; [email protected] 3 Department of Biomedical and Environmental Analyses, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211, 50-556 Wroclaw, Poland * Correspondence: [email protected]; Tel.: +48-71-784-0171 Abstract: Kidney transplantation (KTx) is the best treatment method for end-stage kidney disease. KTx improves the patient’s quality of life and prolongs their survival time; however, not all patients benefit fully from the transplantation procedure. For some patients, a problem is the premature loss of graft function due to immunological or non-immunological factors. Circulating cell-free DNA (cfDNA) is degraded deoxyribonucleic acid fragments that are released into the blood and other body fluids. Donor-derived cell-free DNA (dd-cfDNA) is cfDNA that is exogenous to the patient and comes from a transplanted organ. As opposed to an invasive biopsy, dd-cfDNA can be detected by a non-invasive analysis of a sample. The increase in dd-cfDNA concentration occurs even before the creatinine level starts rising, which may enable early diagnosis of transplant injury and adequate Citation: Martuszewski, A.; treatment to avoid premature graft loss.
    [Show full text]
  • Use of Regulatory T Cells As a Cellular Therapy for Transplant Rejection/Autoimmunity
    American Journal of www.biomedgrid.com Biomedical Science & Research ISSN: 2642-1747 --------------------------------------------------------------------------------------------------------------------------------- Mini Review Copy Right@ Nick D Jones Use of Regulatory T Cells as a Cellular Therapy for Transplant Rejection/Autoimmunity Nick D Jones1* and Renad Alhamawi1,2 1Institute of Immunology and Immunotherapy, University of Birmingham, UK. B15 2TT 2Medical laboratory Technology department, Taibah University, KSA *Corresponding author: Nick D Jones, Institute of Immunology and Immunotherapy, University of Birmingham, B15 2TT, UK. To Cite This Article: Nick D Jones. Use of Regulatory T Cells as a Cellular Therapy for Transplant Rejection/Autoimmunity. Am J Biomed Sci & Res. 2019 - 5(2). AJBSR.MS.ID.000882. DOI: 10.34297/AJBSR.2019.05.000882 Received: August 14, 2019; Published: September 10, 2019 Keywords: Abbreviations: Antigen BAR: specific B cell AntibodyTreg; Autoimmunity; Receptor; CAR: GVHD; Chimeric Treg; TransplantationAntigen Receptor; Foxp3: forkhead box protein 3; GVHD: Graft Versus Host Disease; HSC: Haematopoietic Stem Cell; TCR: T Cell Receptor; Treg: Regulatory T Cell Introduction Treg can be isolated from a number of different sources Foxp3+ regulatory T cells (Treg) are a crucial sub-population including peripheral blood, umbilical cord blood and discarded of T cells in the control of immunity and the maintenance of paediatric thymuses, however, the most common source for Treg immunological tolerance aiding the prevention of autoimmunity. As thus far used in clinical trials is peripheral blood. In order to take such Treg have been proposed to be a candidate cell that could be advantage of the suppressive capacity of such cells and due to the used as cellular therapy to suppress unwanted immune responses.
    [Show full text]
  • Full Prescribing Information Warning
    FULL PRESCRIBING INFORMATION WARNING: ANAPHYLAXIS Antithymocyte globulins can cause anaphylaxis when injected intravenously. Although ATGAM is processed to reduce the level of antibodies that will react to non-T cells, physicians should be prepared for the potential risk of anaphylaxis and monitor patients for signs and symptoms during infusion. 1 INDICATIONS AND USAGE 1.1 Renal Allograft Rejection Renal transplant rejection: ATGAM is indicated for the management of allograft rejection in renal transplant patients; when administered with conventional therapy at the time of rejection ATGAM increases the frequency of resolution of the acute rejection episode [see Clinical Studies (13.1)]. 1.2 Aplastic Anemia ATGAM is indicated for the treatment of moderate to severe aplastic anemia in patients unsuitable for bone marrow transplantation [see Clinical Studies (13.2)]. The usefulness of ATGAM has not been demonstrated in patients with aplastic anemia who are suitable candidates for bone marrow transplantation or in patients with aplastic anemia secondary to neoplastic disease, storage disease, myelofibrosis, Fanconi’s syndrome, or in patients known to have been exposed to myelotoxic agents or radiation. 2 DOSAGE AND ADMINISTRATION ATGAM is intended for intravenous use only. ATGAM is used with concomitant immunosuppressants. During repeat courses of ATGAM, observe patients for signs of allergic reactions [see Warnings and Precautions (5.1)]. 2.1 Dose Renal Allograft Recipients Renal transplant rejection: The recommended dose is 10 to 15 mg/kg daily intravenously for 14 days. Additional alternate-day therapy up to a total of 21 doses may be given. Page 1 of 16 Aplastic Anemia (Moderate to Severe) The recommended dose is 10 to 20 mg/kg daily intravenously for 8 to 14 days.
    [Show full text]
  • Case Report Humoral Acute Rejection in a Kidney Transplant Recipient with Idiopathic Thrombocytopenic Purpura
    Hindawi Case Reports in Transplantation Volume 2021, Article ID 9933354, 4 pages https://doi.org/10.1155/2021/9933354 Case Report Humoral Acute Rejection in a Kidney Transplant Recipient with Idiopathic Thrombocytopenic Purpura Ana Paola Rico-Portillo ,1 José Ignacio Cerrillos-Gutierrez ,1 Jorge Andrade-Sierra ,1 Alfredo Gutiérrez-Govea ,1 Enrique Rojas-Campos ,2 Claudia Alejandra Mendoza-Cerpa ,3 and Benjamín Gómez-Navarro 1 1Departamento de Nefrología y Trasplantes, UMAE, Hospital de Especialidades, CMNO, IMSS, Guadalajara, Jalisco, Mexico 2Unidad de Investigación Médica en Enfermedades Renales UMAE, Hospital de Especialidades, CMNO, IMSS, Guadalajara, Jalisco, Mexico 3Departamento de Anatomía Patológica UMAE, Hospital de Especialidades, CMNO, IMSS, Guadalajara, Jalisco, Mexico Correspondence should be addressed to Alfredo Gutiérrez-Govea; [email protected] Received 29 March 2021; Revised 13 April 2021; Accepted 16 April 2021; Published 23 April 2021 Academic Editor: Ryszard Grenda Copyright © 2021 Ana Paola Rico-Portillo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. A 47-year-old male was diagnosed with chronic kidney disease (CKD) in 2011; idiopathic thrombocytopenic purpura (ITP) was also diagnosed in 2011 refractory to medical treatment and finally treated with splenectomy (2017) without relapses since that date, 5 blood transfusions, and 4 platelet apheresis in 2017. Renal transplant from a living related donor (brother), ABO compatible, crossmatch were negative, sharing 1 haplotype. Donor-specific anti-HLA antibody was negative. Graft function was stable until the 5th day and graft biopsy on the 6th day; thrombotic microangiopathy (TMA), C4D negative and inflammatory infiltration of polymorphonuclear leukocytes inside peritubular capillary, and anti-MICA antibodies were positive.
    [Show full text]