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 transfectants to stimulate murine Th1 clones. Most of the transfectants failed to activate the Th1 clones and, in fact, induced Ag-specific anergy. However, we found that one tumor, a UV-induced fibrosarcoma (6130-VAR1), was capable of stimulating both cytokine production and proliferation in Th1 clones. We believe that 6130-VAR1 cells possess a unique costimulatory activity for the following reasons. First, these cells fail to express known costimulatory molecules including B7-1 and B7-2. Second, 6130-VAR1-mediated stimulation of Th1 clones was not blocked by anti-CD28 Fab or by CTLA4Ig, which suggests that members of the B7 family were not up-regulated during the course of stimulation and that activation does not occur via a CD28-dependent pathway. Third, 6130-VAR1 could provide costimulation when presented on a different surface than the class II/peptide ligand for the TCR. This last finding suggested that the activity on these cells was not simply an adhesion molecule that facilitated increased efficiency of T cell:MHC interactions. Finally, like B7-1 transfectants, stimulation by class II-positive 6130-VAR1 cells prevented the induction of anergy in the Th1 clones. Taken 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.
Zuckerman
L A
LA
Committee on Immunology, University of Chicago, IL 60637, USA.
Sant
A J
AJ
Miller
J
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000276:immunology; D017635:Clonal Anergy / Q000276:immunology; D002999:Clone Cells; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D007376:Interleukin-2 / Q000032:analysis; D051379:Mice; D012709:Serum Albumin / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D018122:B7-1 Antigen; D015815:Cell Adhesion Molecules; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D012709:Serum Albumin; D018799:Intercellular Adhesion Molecule-1