THYMIC STROMA-DERIVED T-CELL INHIBITORY FACTOR (TSTIF) .2. TSTIF ACTSON THE ANTIGEN-PRESENTING CELL TO INHIBIT ANTIGEN-STIMULATED T-CELL PROLIFERATION

Culture supernatant (SN) was obtained from the monolayer of the MRL104 .8a thymic stromal cell clone. This SN alone induced proliferation of helper T-cell (Th) clones because it contained IL-7. However, addition of the SN to cultures of Th stimulated with antigen plus antigen-pres enting cells (APC) resulted in potent inhibition of their proliferatio n. This suppression was ascribed to a factor (designated thymic stroma -derived T-cell inhibitory factor, TSTIF) that is contained in the MRL 104.8a SN and distinct from IL-7. TSTIF affected antigen-stimulated pr oliferation of both type 1 helper (Th1) and type 2 helper (Th2) T-cell clones. The TSTIF effect was also observed by the presence of the MRL 104.8a SN only in the initial 24 hr pre-culture during the entire cou rse (48-72 hr) of antigenic stimulation. Pre-exposure of Th cells to t he SN in the absence of Ag/APC induced their proliferation upon stimul ation with Ag/APC in the next 48 hr cultures. However, pre-cultures of Th cells with the SN in the presence of APC alone (without antigen) r esulted in potent inhibition of the subsequent Ag/APC-stimulated proli feration. Interaction of TSTIF with APC but not with responding Th cel ls was further demonstrated in the following experiment: APC alone wer e exposed to the MRL104.8a SN and used for stimulation of Th that had not been exposed to the SN. Such an APC population exhibited a remarka bly reduced capacity to induce antigen-stimulated Th proliferation whe n compared to that induced by freshly prepared APC or APC cultured in the absence of the MRL104.8a SN. These results indicate that TSTIF exe rts its inhibitory effect on the antigen-stimulated T-cell proliferati on by acting on APC.