IDENTIFICATION OF A UNIQUE COSTIMULATORY ACTIVITY FOR MURINE T-HELPER-1 T-CELL CLONES

We have examined the ability of several class II-positive tumor cell t ransfectants to stimulate murine Th1 clones. Most of the transfectants failed to activate the Th1 clones and, in fact, induced Ag-specific a nergy. However, we found that one tumor, a UV-induced fibrosarcoma (61 30-VAR1), was capable of stimulating both cytokine production and prol iferation in Th1 clones. We believe that 6130-VAR1 cells possess a uni que costimulatory activity for the following reasons. First, these cel ls fail to express known costimulatory molecules including B7-1 and B7 -2. Second, 6130-VAR1-mediated stimulation of Th1 clones was not block ed by anti-CD28 Fab or by CTLA4lg, which suggests that members of the B7 family were not up-regulated during the course of stimulation and t hat activation does not occur via a CD28-dependent pathway. Third, 613 0-VAR1 could provide costimulation when presented on a different surfa ce than the class II/peptide ligand for the TCR. This last finding sug gested that the activity on these cells was not simply an adhesion mol ecule that facilitated increased efficiency of T cell:MHC interactions . Finally, like B7-1 transfectants, stimulation by class It-positive 6 130-VAR1 cells prevented the induction of anergy in the Th1 clones. Ta ken together, these results strongly suggest that 6130-VAR1 expresses a unique costimulatory activity (VAM-1) that, like B7-1, can promote T cell activation and prevent anergy induction.