The mechanisms by which MHC interactions continually modulate the peripheral T cell repertoire are poorly understood. CD8 T cells that express TCRs which fail to co-engage class I normally undergo rapid apoptosis following an apparent loss Of CTL cytolytic activity. Mis-selected CD8 T cells are inactivated via inhibition of an activation process normally regulated by the transcription factor lung Kruppel-like factor (LKLF). We propose to examine the role of the co-receptor MHC interactions in mediating disregulated T cell receptor (TCR) signaling and effector function. Preliminary experiments conducted with CD8 cells in the b2m-/- murine model has indicated that CD8 cells deprived of class I signals undergo CD3z downregulation. In addition the CTL suppressor cytokines, IL10 and TGFb are significantly upregulated. We hypothesize that normally selected CD8 cells undergo a similar process of inactivation when deprived of MHC class I interactions. It is important to determine the contribution of such cells to a normal immune response.
| Trimble, Linda A; Prince, Kenya A; Pestano, Gary A et al. (2002) Fas-dependent elimination of nonselected CD8 cells and lpr disease. J Immunol 168:4960-7 |
