A RADIOSENSITIVE APC ACTIVITY DISSOCIATES IL-2 SECRETION AND ACTIVATION-INDUCED CELL-DEATH BY AUTOREACTIVE T-CELL HYBRIDOMAS

T cell hybridomas were generated from a LEW rat T cell line specific f or the uveitogenic peptide bov-B1 of bovine retinal S-antigen. Using t hese autoreactive hybridomas, IL-2 production and activation-induced c ell death (AICD) were dissociated as outcomes of activation. The self- reactive hybridomas secrete IL-2 and undergo AICD in response to antig en presented by non-irradiated syngeneic splenocytes, whereas antigen presentation by irradiated splenocytes induced only AICD, IL-2 product ion by a non-self reactive hybridoma was unaffected by irradiation of the APC. Pretreatment of the APC with phorbol ester or lipopolysacchar ide and IL-4 protected their ability to induce IL-2 secretion after ga mma-irradiation. Although the co-stimulation-blocking reagent CTLA-4-I g mimicked the effect of gamma-irradiation by preventing IL-2 secretio n but not AICD, B7 expression on the APC was not radiosensitive, nor d id co-stimulation, provided 'in trans' with a B7-expressing third-part y cell, reconstitute antigen-specific hybridoma IL-2 secretion in resp onse to irradiated APC, In summary, the data show that IL-2 secretion and AICD of a self-reactive T cell hybridoma can be dissociated as con sequences of TCR occupancy in the presence of a functional co-stimulat ory signal. It is proposed that the signals producing these events are transduced through the TCR-CD3 complex alone and reflect the differen tial outcomes of high- and low-affinity interactions.