La. Zuckerman et al., IDENTIFICATION OF A UNIQUE COSTIMULATORY ACTIVITY FOR MURINE T-HELPER-1 T-CELL CLONES, The Journal of immunology, 154(9), 1995, pp. 4503-4512
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.