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Langerhans Cells Dendritic Cells Is a Direct Precursor of Subset of Human Blood + /Cd11c + a Cd1a

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Langerhans Cells Dendritic Cells Is a Direct Precursor of Subset of Human Blood + /Cd11c + a Cd1a A CD1a+/CD11c+ Subset of Human Blood Dendritic Cells Is a Direct Precursor of Langerhans Cells This information is current as Tomoki Ito, Muneo Inaba, Kayo Inaba, Junko Toki, Shinji of October 2, 2021. Sogo, Tomoko Iguchi, Yasushi Adachi, Kazuyuki Yamaguchi, Ryuichi Amakawa, Jenny Valladeau, Sem Saeland, Shirou Fukuhara and Susumu Ikehara J Immunol 1999; 163:1409-1419; ; http://www.jimmunol.org/content/163/3/1409 Downloaded from References This article cites 40 articles, 23 of which you can access for free at: http://www.jimmunol.org/content/163/3/1409.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 October 2, 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 © 1999 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. A CD1a1/CD11c1 Subset of Human Blood Dendritic Cells Is a Direct Precursor of Langerhans Cells1 Tomoki Ito,*† Muneo Inaba,† Kayo Inaba,‡ Junko Toki,† Shinji Sogo,§ Tomoko Iguchi,*† Yasushi Adachi,† Kazuyuki Yamaguchi,* Ryuichi Amakawa,* Jenny Valladeau,¶ Sem Saeland,¶ Shirou Fukuhara,* and Susumu Ikehara2* Based on the relative expression of CD11c and CD1a, we have identified three fractions of dendritic cells (DCs) in human peripheral blood, including a direct precursor of Langerhans cells (LCs). The first two fractions were CD11c1 DCs, comprised of a major CD1a1/CD11c1 population (fraction 1), and a minor CD1a2/CD11c1 component (fraction 2). Both CD11c1 fractions displayed a monocyte-like morphology, endocytosed FITC-dextran, expressed CD45RO and myeloid markers such as CD13 and CD33, and possessed the receptor for GM-CSF. The third fraction was comprised of CD1a2/CD11c2 DCs (fraction 3) and resembled plasmacytoid T cells. These did not uptake FITC-dextran, were negative for myeloid markers (CD13/CD33), Downloaded from and expressed CD45RA and a high level of IL-3Ra, but not GM-CSF receptors. After culture with IL-3, fraction 3 acquired the characteristics of mature DCs; however, the expression of CD62L (lymph node-homing molecules) remained unchanged, indi- cating that fraction 3 can be a precursor pool for previously described plasmacytoid T cells in lymphoid organs. Strikingly, the CD1a1/CD11c1 DCs (fraction 1) quickly acquired LC characteristics when cultured in the presence of GM-CSF 1 IL-4 1 TGF-b1. Thus, E-cadherin, Langerin, and Lag Ag were expressed within 1 day of culture, and typical Birbeck granules were 2 1 2 2 observed. In contrast, neither CD1a /CD11c (fraction 2) nor CD1a /CD11c (fraction 3) cells had the capacity to differ- http://www.jimmunol.org/ entiate into LCs. Furthermore, CD141 monocytes only expressed E-cadherin, but lacked the other LC markers after culture in these cytokines. Therefore, CD1a1/CD11c1 DCs are the direct precursors of LCs in peripheral blood. The Journal of Immunology, 1999, 163: 1409–1419. endritic cells (DCs)3 are bone marrow-derived profes- of epidermal LCs. The other pathway includes a CD1a2/CD141 sional APCs that initiate and regulate immune responses intermediate that can differentiate into monocyte-derived or dermal D (1–3). Recent studies have demonstrated that DCs in situ DCs that lack LC markers. GM-CSF and TNF-a are required in can exist in different maturational states and pathways of differ- both pathways, but TGF-b1 is found to be important for the for- entiation. Subtypes of DCs with some differences in morphology, mation of Birbeck granules and Lag Ag of LCs (20–22). It has also by guest on October 2, 2021 phenotype, and function include interdigitating cells in lymphoid been found that peripheral blood monocytes cultured with a com- organs (4), peripheral blood DCs (5, 6), Langerhans cells (LCs) in bination of GM-CSF, IL-4, and TNF-a differentiate into mature the epidermis of the skin (7, 8), dermal DCs (9, 10), and thymic DCs (23), and that LCs may develop if TGF-b1 is added (24). The DCs (11, 12). In the human tonsil, DCs in the germinal center (13) identification of DC intermediates in the peripheral blood is, there- and plasmacytoid T cells in the T cell zones (14) have recently fore, important, because it is thought that most blood DCs are been identified as new DC subsets. either en route from the bone marrow to peripheral tissues, or from Hemopoietic progenitors that differentiate into various types of nonlymphoid tissues to the regional lymph nodes and spleen. DCs are present in the cord blood (15, 16), bone marrow (17), and Previously, DCs were purified from the peripheral blood after a peripheral blood (18, 19). At least two separate developmental 1- to 2-day culture period. These DCs were morphologically, phe- 1 pathways of DCs from CD34 progenitors have been shown (16, notypically, and functionally different from the DCs present in the 1 2 19): one pathway involves CD1a /CD14 cells with the features circulation (25, 26). Recently, DCs have been isolated from the peripheral blood by immunoselection methods without culture. DCs thus prepared are not the morphologically typical DCs, and, † *First Department of Internal Medicine and First Department of Pathology, Kansai interestingly, there are two subsets with distinct phenotype (27– Medical University, Moriguchi, Osaka, Japan; ‡Department of Zoology, Kyoto Uni- versity, Sakyo, Kyoto, Japan; §Cellular Technology Institute, Otsuka Pharmaceutical 29). The nature, origin, and commitment of these DCs require Co., Tokushima, Japan; and ¶Schering-Plough, Laboratory for Immunological Re- further analysis. In the present study, we have isolated fractions of search, Dardilly, France blood DCs using magnetic beads and a multicolor sorting system. Received for publication January 11, 1999. Accepted for publication May 20, 1999. We have distinguished three distinct fractions by extensive surface The costs of publication of this article were defrayed in part by the payment of page marker analyses, and have examined their functions and develop- charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. mental capacities. During these investigations, we have identified 1 This work was supported by a grant from the Ministry of Health and Welfare’s a distinct subset of DCs that quickly differentiates into LCs. Study Group on Specific Diseases Research and by grants from the Ministry of Ed- Strunk et al. have reported that, in the peripheral blood, only ucation, Science, and Culture, and the Japan Private School Promotion Foundation. CD341 progenitors expressing the skin-homing receptor differen- 2 Address correspondence and reprint requests to Dr. Susumu Ikehara, First Depart- tiate into LCs (after 10- to 18-day culture) (19). It has recently ment of Pathology, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi City, b Osaka 570-8506, Japan. E-mail address: [email protected] been reported that, in the presence of GM-CSF, IL-4, and TGF- 1 1 3 Abbreviations used in this paper: DC, dendritic cell; EM, electron microscope; LC, for 6 days, human peripheral blood monocytes (CD14 cells) can Langerhans cell; PerCP, peridini-chlorophyll protein; PI, propidium iodide. differentiate into LCs characterized by the expression of CD1a, Copyright © 1999 by The American Association of Immunologists 0022-1767/99/$02.00 1410 LC PRECURSORS IN HUMAN PERIPHERAL BLOOD Table I. Abs used for phenotypical analysisa Clone Isotype Source Clone Isotype Source CD1a BB-5 IgG1 TAG CD42b SZ2 IgG1 IM CD1a BL-6 IgG1 IM CD44 F10-44-2 IgG2a Serotec CD1c M241 IgG1 ANC CD45 HI30 IgG1 PM CD2 T11 IgG1 C CD45RA 2H4 IgG1 C CD3 Leu-4 IgG1 BD CD45RO UCHL1 IgG2a IM CD3 M2AB IgG1 EXA CD49d HP2/1 IgG1 IM CD3 UCHT1 IgG1 PM CD49e SAM1 IgG2b IM CD4 Leu-3a IgG1 BD CD50 HP2/19 IgG2a IM CD4 7E14 IgG1 EXA CD54 Leu-54 IgG2b BD CD5 T1 IgG2a C CD54 D3.6 IgG2b EXA CD5 M28623 IgG2a EXA CD56 Leu-19 IgG1 BD CD7 3A1 IgG2b C CD61 SZ21 IgG1 IM CD7 G34 IgG2a EXA CD62L TQ-1 IgG1 C CD8 T8 IgG1 C CD62P CLBThromb/6 IgG1 IM CD9 C3-3A2 IgG1 ANC CD64 10.1 IgG1 PM CD10 J5 IgG2a C CD68 KP-1 IgG1 Dako CD11a HI111 IgG1 PM CD70 BU69 IgG1 ANC CD11b ICRF(44) IgG1 PM CD71 LO1.1 IgG2a BD CD11b Mo1 IgM C CD72 J4-117 IgG2a PM Downloaded from CD11c Leu-M5 IgG2b BD CD80 BB-1 IgM ANC CD11c 3.9 IgG1 Serotec CD83 HB15a IgG2b IM CD13 WM15 IgG1 PM CD86 IT2.2 IgG2b PM CD14 Leu-M3 IgG2b BD CD90 5E10 IgG1 PM CD14 FWKW-1 IgG2b EXA CD95(FAS) UB2 IgG1 MBL CD14 UCHM1 IgG2a ANC CD103 2G5 IgG2a IM CD15 80H5 IgM IM CD114(G-CSFR) LMM741 IgG1 PM CD15s 2H5 IgM PM CD116(GM-CSFR) M5D12 IgM PM http://www.jimmunol.org/ CD16 Leu-11a IgG1 BD CD117(C-KIT) 95C3 IgG1 IM CD16 J5511 IgG1 EXA CD121a(IL-1R 1) 6B5 IgG2a PM CD16 3G8 IgG1 PM CD122(IL-2Rb) TIC-1 IgG1 END CD18 L130 IgG1 BD CD123(IL-3Ra) 9F5 IgG1 PM CD19 B4 IgG1 C CD130 AM64 IgG1 PM CD19 1G9 IgG1 EXA CD135(Flt3) SF1.340 IgG1 IM CD19 HIB19 IgG1 PM CD152(CTLA-4) BNI3 IgG2a IM CD20 B1 IgG2a C CD154(CD40L) 24-31 IgG1 ANC CD21 BL13 IgG1 IM E-cadherin HECD-1 IgG1 Takara CD23 9P25 IgG1 IM CLA HECA-452 RatIgM PM by guest on October 2, 2021 CD25(IL-2Ra) 2A3 IgG1 BD Lag IgG1 Dr.
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