DIFFERENTIAL RESPONSE OF CD4(-) CELLS TO T-CELL RECEPTOR-DEPENDENT SIGNALS - CD4(+) V7(+) T-CELLS ARE CO-STIMULATION INDEPENDENT AND ANTI-V7 ANTIBODY BLOCKS THE INDUCTION OF ANERGY BY BACTERIAL SUPERANTIGEN() V7(+) AND CD4(+) V7()

V7 is a novel cell surface glycoprotein that is expressed on 25 % of c irculating T lymphocytes. This molecule appears to play a critical rol e in T cell activation based on the observation that a monoclonal anti -V7 antibody inhibits T cell receptor (TCR)-dependent interleukin-2 (I L-2) production and proliferation of T cells. In the current study, CD 4(+)V7(+) and CD4(+)V7(-) T cells were separated from one another and their response to various stimuli analyzed. Although there were only m inor differences between the two subsets in the expression of activati on/differentiation markers, including CD45RA and RO isotypes, when exp osed to immobilized anti-CD3 or anti-TCR antibodies in the absence of APC, CD4(+)V7(+) T cells alone produced IL-2 and proliferated vigorous ly. By contrast, CD4(+)V7(-) cells responded poorly to such stimuli, b ut they recovered their capacity to respond if antigen-presenting cell s (APC) or anti-CD28 antibody were added to the cultures. The enhancem ent of the V7(-) T cell response by APC appears to be related to augme ntation of TCR signals because the effect could be blocked by antibodi es against molecules on APC [major histocompatibility (MHC) class II, CD86] that are known to up-regulate such signals through their interac tion with counter-receptors on T cells. To assess the role of V7 in a system independent of co-stimulation, CD4(+) T cells were stimulated w ith the bacterial superantigens, staphylococcal enterotoxins A and B. The cells responded by proliferating and then becoming anergic. Additi on of anti-V7 antibody at the initiation of culture with superantigen did not inhibit cellular proliferation but prevented T cells from beco ming anergic, while addition of anti-CD28 antibody had no effect on ei ther proliferation or anergy induction. These results indicate that V7 and CD28 mediate distinct intracellular signals and suggest that V7 f unctions to preserve T cell reactivity whether the stimulus is mitogen ic or anergizing.