Dendritic cells in transplantation - Friend or foe?

被引:242
作者
Lechler, R
Ng, WF
Steinman, RM
机构
[1] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Sch Med, Dept Immunol,Div Med, London W12 0NN, England
[2] Rockefeller Univ, Cellular Physiol & Immunol Lab, New York, NY 10021 USA
关键词
D O I
10.1016/S1074-7613(01)00116-9
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The existence of two sets of dendritic cells in transplantation (of donor and recipient origin) poses unique problems in alloimmunity and tolerance. Donor DCs are potent stimulators of the direct pathway, in which recipient T cells respond to peptides presented on donor MHC products or to the donor MHC molecules themselves. Reduced DC function in the direct pathway is used to explain the acceptance of certain allografts that have been depleted of passenger leukocytes. Reciprocally, purified donor DCs powerfully stimulate the rejection of these grafts as well as the mixed leukocyte reaction by purified allogeneic T cells in culture. Donor DCs also can act as specialized antigen transport vehicles in cross-priming for the indirect pathway. Here, recipient DCs process MHC molecules from the donor. The indirect pathway of rejection is actually the rule for passenger leukocyte-depleted grafts. Furthermore, the indirect pathway seems to be the dominant alloresponse detected in long-term graft recipients, both in experimental models and clinical transplantation, particularly in those with chronic rejection. The stimulatory function of DCs in both direct and indirect pathways is regulated by their maturation in response to inflammatory stimuli, especially those delivered via IL-1, TNF, and Toll receptor families. Since the normal function of DCs is to generate immunity against invading pathogens, the indirect response to peptides continually derived from the allogeneic MHC molecules in a tissue allograft (a surgically introduced "pathogen" because of the associated inflammation and necrosis) may be more difficult to silence. However, in addition to their allostimulatory role, immature or in vitro-manipulated DCs also have the potential to downregulate direct and indirect antidonor responses through a variety of mechanisms. Intriguing new evidence shows that immature DCs can actively induce regulatory T cells. Given the probable role of the indirect pathway in driving chronic rejection, the induction of T cell tolerance (deletion, anergy, and regulation), especially in those T cells with indirect antidonor allospecificity, by the injection of immature DCs pretransplant, could serve as a critical therapeutic strategy.
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收藏
页码:357 / 368
页数:12
相关论文
共 79 条
  • [1] CD4+ T cell tolerance to parenchymal self-antigens requires presentation by bone marrow-derived antigen-presenting cells
    Adler, AJ
    Marsh, DW
    Yochum, GS
    Guzzo, JL
    Nigam, A
    Nelson, WG
    Pardoll, DM
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1998, 187 (10) : 1555 - 1564
  • [2] Dendritic cells acquire antigen from apoptotic cells and induce class I restricted CTLs
    Albert, ML
    Sauter, B
    Bhardwaj, N
    [J]. NATURE, 1998, 392 (6671) : 86 - 89
  • [3] Major histocompatibility complex class I peptide-pulsed host dendritic cells induce antigen-specific acquired thymic tolerance to islet cells
    Ali, A
    Garrovillo, M
    Jin, MX
    Hardy, MA
    Oluwole, SF
    [J]. TRANSPLANTATION, 2000, 69 (02) : 221 - 226
  • [4] Antigen processing and presentation in transplantation
    Auchincloss, H
    Sultan, H
    [J]. CURRENT OPINION IN IMMUNOLOGY, 1996, 8 (05) : 681 - 687
  • [5] BAKER RJ, 2001, IN PRESS TRANSPLANTA
  • [6] ROLE OF AFFERENT LYMPHATICS IN REJECTION OF SKIN HOMOGRAFTS
    BARKER, CF
    BILLINGHAM, RE
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1968, 128 (01) : 197 - +
  • [7] Vigorous allograft rejection in the absence of danger
    Bingaman, AW
    Ha, J
    Waitze, SY
    Durham, MM
    Cho, HR
    Tucker-Burden, C
    Hendrix, R
    Cowan, SR
    Pearson, TC
    Larsen, CP
    [J]. JOURNAL OF IMMUNOLOGY, 2000, 164 (06) : 3065 - 3071
  • [8] BOWEN K M, 1980, Diabetes, V29, P98
  • [9] SPECIFICITY AND PROMISCUITY AMONG NATURALLY PROCESSED PEPTIDES BOUND TO HLA-DR ALLELES
    CHICZ, RM
    URBAN, RG
    GORGA, JC
    VIGNALI, DAA
    LANE, WS
    STROMINGER, JL
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1993, 178 (01) : 27 - 47
  • [10] Acquired systemic tolerance to rat cardiac allografts induced by intrathymic inoculation of synthetic polymorphic MHC class I allopeptides
    Chowdhury, NC
    Murphy, B
    Sayegh, MH
    Jin, MX
    Roy, DK
    Hardy, MA
    Oluwole, SF
    [J]. TRANSPLANTATION, 1996, 62 (12) : 1878 - 1882