CD4 T cell-mediated cardiac allograft rejection requires donor but not host MHC class II

J Clin Invest. 2000 Oct;106(8):1003-10. doi: 10.1172/JCI10467.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Disease
  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • Genes, MHC Class II*
  • Graft Rejection / immunology*
  • H-2 Antigens
  • Heart Transplantation / immunology*
  • Heart Transplantation / mortality
  • Histocompatibility Antigens Class II / immunology*
  • Isoantibodies
  • Lymphocyte Culture Test, Mixed
  • Lymphocyte Depletion
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, SCID / immunology
  • Transplantation, Homologous


  • H-2 Antigens
  • Histocompatibility Antigens Class II
  • Isoantibodies