Activation requirements of 2,4-dinitrobenzenesulfonate-primed T suppressor cells

Culture of spleen cells from mice tolerized with 2,4-dinitrobenzenesulfonate (DNBS) with DNP-labeled spleen cells (DNP-SC) activates Lyt 2/sup +/ Ts to synthesize and release a suppressor factor (SSF) into the supernatant (SN) which suppresses the transfer of contact sensitivity to 2,4-dinitrofluorobenzene. Activation of the Ts requires recognition of DNP in association with class I MHC determinants. The signals which activate these Ts to produce SSF were examined in greater detail. The SN from cultures of L3T4-depleted tolerant cells and DNP-SC did not contain SSF activity, suggesting that an L3T4/sup +/ cell was required for Ts activation. Similarly, the SN from cultures of DNBS-primed cells and gluteraldehyde-fixed (Glu-) DNP-SC had no SSF activity. Addition of Il-1 restored the ability of the Ts to synthesize and release the factor into the SN in both cases. By contrast to the SN, the soluble cell lysate from cultures of tolerant cells and Glu-DNP-SC, or from L3T4-depleted tolerance cells and DNP-SC did contain the SSF activity. These results indicate that two signals are required to activate DNBS-primed Ts to produce SSF. Recognition of DNP/class I MHC stimulates the Ts to synthesize SSF and a costimulator is required for release of the factor. These results furthermore » indicate that the L3T4-bearing cells play no role in the synthesis of SSF. Rather, these cells induce the costimulator which is required for factor release.« less