FUNCTIONAL DEFECTS ARE ASSOCIATED WITH ABNORMAL SIGNAL-TRANSDUCTION IN T-CELLS OF MICE INOCULATED WITH PARENTAL BUT NOT IL-2 SECRETING TUMOR-CELLS

CMS5, a murine fibrosarcoma, was transduced with the IL-2 gene to stim ulate the host antitumor response. Previously, we described that splen ocytes isolated from parental rumor bearing (ITB) mice and IL-2-secret ing tumor bearing (ITB) mice differed significantly in their prolifera tive responses when restimulated with IL-2-secreting tumor cells. In t his report we extend these results by showing that the inability of PT B cells to proliferate when stimulated with parental CMS5 cells is not corrected by providing a source of costimulation. Furthermore, we dem onstrate that T cells from PTB animals exhibit defective signaling thr ough the T-cell receptor, defined by decreased protein tyrosine phosph orylation, that correlates with the impairment of functions attributed to both CD4(+) and CD8(+) T cells. In contrast, T cells from ITB anim als are normal in this regard. The results suggest that immunosuppress ion underlies functional differences between PTB and ITB splenocytes a nd that defects in signal transduction may be responsible for the lack of normal functional responses.