Cellular mechanisms of graft rejection mediated by CD4-CD8-TCR alphabeta T cells.

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Generation of in vitro CD4^-CD8^-TCR alphabeta CTL response against allogeneic MHC class I antigen and MHC class I-restricted antigen was investigated. We demonstrated that in mice that were depleted of CD8^+ cells, CD4^-CD8^-TCR alphabeta CTL were induced against allogeneic MHC class I antigen following activation of CD4^+ cells. On the other hand, against MHC-class I restricted antigen, CD8-depleted mice were incapable of generating CTL response. However, when target cells were MHC class II (and I) antigen positive cells, CTL with both CD4^+ and CD4^-CD8^-TCR alphabeta phenotypes were generated in CD8-depleted B6 mice. Thus, in this case, stimulation of CD4^+ T cells by MHC class II restricted antigen leads to generation of CD4^-CD8^-TCR alphabeta CTL specific for MHC class I restricted antigen. Moreover, CD4^-CD8^-TCR alphabeta CTL are capable of mediating rejection responses in vivo.