CD4 T cell-mediated cardiac allograft rejection requires donor but not host MHC class II.
Numerous studies indicate that CD4 T cells are required for acute cardiac allograft rejection. However, the precise role for CD4 T cells in this response has remained ambiguous owing to the multipotential properties of this T-cell subpopulation. In the current study, we demonstrate the capacity of CD4 T cells to serve as direct effector cells of cardiac allograft rejection. We show that CD4 T cells are both necessary and sufficient for acute graft rejection, as indicated by adoptive transfer experiments in immune-deficient SCID and rag1(-/-) recipients. We have analyzed the contribution of direct (donor MHC class II restricted) and indirect (host MHC class II restricted) antigen recognition in CD4-mediated rejection. Acute CD4 T cell-mediated rejection required MHC class II expression by the allograft, indicating the importance of direct graft recognition. In contrast, reciprocal experiments indicate that CD4 T cells can acutely reject allogeneic cardiac allografts established in rag1(-/-) hosts that were also MHC class II deficient. This latter result indicates that indirect presentation of donor antigens by host MHC class II is not required for acute CD4-mediated rejection. Taken together, these results indicate that CD4 T cells can serve as effector cells for primary acute cardiac allograft rejection, predominantly via direct donor antigen recognition and independent of indirect reactivity.
Pietra
B A
BA
Division of Cardiology, The Children's Hospital, Barbara Davis Center for Childhood Diabetes, Denver, CO 80262, USA.
Wiseman
A
A
Bolwerk
A
A
Rizeq
M
M
Gill
R G
RG
D000208:Acute Disease; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005802:Genes, MHC Class II; D006084:Graft Rejection / Q000276:immunology*; D006183:H-2 Antigens; D016027:Heart Transplantation / Q000276:immunology* / Q000401:mortality; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007518:Isoantibodies; D007959:Lymphocyte Culture Test, Mixed; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID / Q000276:immunology; D014184:Transplantation, Homologous
D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; D007518:Isoantibodies