期刊
TRANSPLANTATION
卷 83, 期 7, 页码 931-937出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/01.tp.0000257960.07783.e3
关键词
direct allorecognition; helper CD4 T cells; alloantibody; CD8 effector cells
资金
- Wellcome Trust Funding Source: Medline
Background. The relative contributions of the direct and indirect pathways of CD4 T cell allorecognition in providing help for generating effective humoral and CD8 T cell alloimmunity remain unclear. Here, the generation of alloantibody and cytotoxic CD8 T cell responses to a vascularized allograft were examined in a murine adoptive-transfer model in which help could only be provided by transferred CD4 T cells recognizing alloantigen exclusively through the direct pathway. Methods. Rejection kinetics and the development of alloantibody and cytotoxic CD8 T cell responses to MHC-mismatched H-2(d) heart grafts were compared when CD4 T cell help was present (wild-type H-2(b) recipients), or absent (CD4 T cell deficient, MHC class II-/- H-2(b) recipients [B6CII(-/-)]), or available only through the direct pathway (B6CII(-/-) mice reconstituted with wild-type CD4 T cells). Results. BALB/c allografts were rejected by B6 mice rapidly (median survival time [MST] 7 days) with strong CD8 T cell effector and alloantibody responses, but were rejected by B6CII(-/-) mice more slowly (MST 23 days), with markedly reduced CD8 T cell responses and no detectable alloantibody. CD4 T cell reconstitution of B6CII(-/-) recipients accelerated heart graft rejection to near that of wild-type recipients (MST 13 days), with complete restoration of cytotoxic CD8 T cell responses but without detectable IgM or IgG alloantibody. Conclusions. Different pathways of helper T cell allorecognition are responsible for generating humoral and CD8 T cell alloimmunity. CD4 T cell help provided exclusively through the direct pathway generates strong cytotoxic CD8 T cell responses that effect rapid heart graft rejection.
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