Direct evidence for in vivo induction of CD8+ cytotoxic T cells directed to donor MHC class I peptides following mouse allotransplantation.
There is accumulating evidence indicating that the T cell response to donor major histocompatibility complex (MHC) peptides plays a crucial role in graft rejection. We and others previously demonstrated the involvement of MHC class-II-restricted recognition of donor MHC class I and II peptides by alloreactive CD4+ T helper cells in graft rejection. Here we studied the in vivo induction of CD8+ cytotoxic T lymphocytes (CTL) directed to donor MHC class I peptides following allotransplantation in the mouse. To address this question, BALB/c irradiated splenocytes (H-2d) (Kd, A(d), E(d), Ld, Dd) were injected into Ld-deficient BALB/c-dm2 (dm2) mutant mice (Kd, A(d), E(d), -, Dd). Nine days after allogeneic cell transplant, recipient lymph node T cells were tested for cytolytic activity using peritoneal macrophages as targets. We observed that in addition to BALB/c targets, dm2 macrophages could also be lysed but only when incubated with a dominant peptide on donor Ld molecule, Ld 61-80. This response was abolished by anti-CD8 but not anti-CD4 monoclonal antibodies. In addition, after immunization of dm2 mice with the peptide Ld 61-80, alloreactive CTL were generated in vivo and shown to destroy allogeneic donor BALB/c target cells in the absence of exogenously added peptide. We conclude that after allotransplantation, concomitant in vivo priming of alloreactive CD8+ CTL by donor MHC class I peptides occurs through both direct and indirect pathways of allorecognition.
Department of Surgery, University of California San Francisco 94143-0508, USA.
I A
IA
Popov
E V
EV
Fedoseyeva
P L
PL
Orr
M R
MR
Garovoy
G
G
Benichou
D000818:Animals; D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D017690:Cell Transplantation; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014184:Transplantation, Homologous / Q000276:immunology*
D015395:Histocompatibility Antigens Class I