A central role for peripheral dendritic cells in the induction of acquired thymic tolerance

被引:66
作者
Goldschneider, I [1 ]
Cone, RE [1 ]
机构
[1] Univ Connecticut, Sch Med, Ctr Hlth, Dept Pathol, Farmington, CT 06030 USA
关键词
D O I
10.1016/S1471-4906(02)00038-8
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Despite extensive negative selection in the thymus, numerous clones of self-reactive T cells are normally exported to the periphery. In most instances, autoimmunity is prevented by regulatory T (Tr) cells, many of which are also of recent thymic origin. We have demonstrated recently that natural killer (NK) Tr thymocytes (THYr) can be induced by the injection of antigen into the eye, an immunologically privileged site; and that the intravenous infusion of antigen-presenting cells (APCs) from such animals also induces NKT THYr. Furthermore, we have also observed that some of these APCs migrate to the thymus as CD11c(+) dendritic cells (DCs). Other authors have correlated the migration of DCs to the thymus with the generation of CD4(+)CD25(+) THYr. We therefore propose a novel tolerance induction pathway by which tolerogenic DCs routinely transport antigen (both self and nonself) from the periphery to the thymus, where they positively select THYr. We also propose that the ability of tolerogenic DCs to induce acquired thymic tolerance on demand might have important implications for the immunotherapy of autoimmunity and allotransplantation.
引用
收藏
页码:77 / 81
页数:5
相关论文
共 61 条
[1]   REENTRY OF T-CELLS TO THE ADULT THYMUS IS RESTRICTED TO ACTIVATED T-CELLS [J].
AGUS, DB ;
SURH, CD ;
SPRENT, J .
JOURNAL OF EXPERIMENTAL MEDICINE, 1991, 173 (05) :1039-1046
[2]   Projection of an immunological self shadow within the thymus by the aire protein [J].
Anderson, MS ;
Venanzi, ES ;
Klein, L ;
Chen, ZB ;
Berzins, SP ;
Turley, SJ ;
von Boehmer, H ;
Bronson, R ;
Dierich, A ;
Benoist, C ;
Mathis, D .
SCIENCE, 2002, 298 (5597) :1395-1401
[3]   On the ontogeny and physiology of regulatory T cells [J].
Annacker, O ;
Pimenta-Araujo, R ;
Burlen-Defranoux, O ;
Bandeira, A .
IMMUNOLOGICAL REVIEWS, 2001, 182 :5-17
[4]   Phenotype, localization, and mechanism of suppression of CD4+CD25+ human thymocytes [J].
Annunziato, F ;
Cosmi, L ;
Liotta, F ;
Lazzeri, E ;
Manetti, R ;
Vanini, V ;
Romagnani, P ;
Maggi, E ;
Romagnani, S .
JOURNAL OF EXPERIMENTAL MEDICINE, 2002, 196 (03) :379-387
[5]   Mouse CD1-specific NK1 T cells: Development, specificity, and function [J].
Bendelac, A ;
Rivera, MN ;
Park, SH ;
Roark, JH .
ANNUAL REVIEW OF IMMUNOLOGY, 1997, 15 :535-562
[6]   Human thymus contains IFN-α-producing CD11c-, myeloid CD11c+ and mature interdigitating dendritic cells [J].
Bendriss-Vermare, N ;
Barthélémy, C ;
Durand, I ;
Bruand, C ;
Dezutter-Dambuyant, C ;
Moulian, N ;
Berrih-Aknin, S ;
Caux, C ;
Trinchieri, G ;
Brière, F .
JOURNAL OF CLINICAL INVESTIGATION, 2001, 107 (07) :835-844
[7]  
Beschorner WE, 1995, TRANSPLANTATION, V60, P1326
[8]   In situ tolerance within the central nervous system as a mechanism for preventing autoimmunity [J].
Brabb, T ;
von Dassow, P ;
Ordonez, N ;
Schnabel, B ;
Duke, B ;
Goverman, J .
JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 192 (06) :871-880
[9]   Targeted expression of major histocompatibility complex (MHC) class II molecules demonstrates that dendritic cells can induce negative but not positive selection of thymocytes in vivo [J].
Brocker, T ;
Riedinger, M ;
Karjalainen, K .
JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 185 (03) :541-550
[10]   THE FAILURE OF INTRATHYMIC TRANSPLANTATION OF NONIMMUNOGENIC ISLET ALLOGRAFTS TO PROMOTE INDUCTION OF DONOR-SPECIFIC UNRESPONSIVENESS [J].
CAMPOS, L ;
POSSELT, AM ;
DELI, BC ;
MAYO, GL ;
PETE, K ;
BARKER, CF ;
NAJI, A .
TRANSPLANTATION, 1994, 57 (06) :950-953