REDUCED CD3-MEDIATED PROTEIN-TYROSINE PHOSPHORYLATION IN ANERGIC CD4-CELLS( AND CD8+ T)

Mice inoculated i.v. with superantigens exhibit long lived Ag-specific T cell tolerance. An in vitro model for this phenomenon is the ensuin g unresponsiveness of Th1 T cell clones activated via the TCR/CD3 comp lex in the absence of costimulation. We have previously demonstrated a lterations in TCR-mediated early protein tyrosine phosphorylation even ts in Th1 clones anergic for IL-2 production. In this study, we demons trate unresponsiveness in CD4+ and CD8+ T cells from Vbeta8.1 transgen ic mice inoculated i.v. with the superantigen Mls-1a. The unresponsive ness of both CD4+ and CD8+ T cells involves defective IL-2 production upon restimulation, with CD4+ T cells exhibiting an additional defect in IL-2 utilization. The transgenic model allowed study of T cell sign aling in a relatively homogeneous population of unresponsive cells wit hout elaborate purification of Ag-reactive populations. Both CD4+ and CD8+ T cells exhibit altered tyrosine phosphorylation of two protein s ubstrates upon CD3-mediated restimulation. The substrates involved, p3 8 and p75, are of identical size to substrates similarly affected in a nergic Th1 clones. Altered tyrosine phosphorylation is therefore close ly associated with defective IL-2 production in these three anergic T cell types, and may play a role in the maintenance of anergy.