CD44 PLAYS A COSTIMULATORY ROLE IN MURINE T-CELL ACTIVATION - LIGATION OF CD44 SELECTIVELY CO-STIMULATES IL-2 PRODUCTION, BUT NOT PROLIFERATION IN TCR-STIMULATED MURINE T(H)1 CELLS

The murine CD44 receptor family is thought to be involved in a variety of lymphocyte functions, including lymphopoesis, lymphocyte homing and cell migration, Herein, we show that murine CD44 also plays a role as a co-stimulatory molecule for the activation of CD4(+) T cells, Ligation of CD44 by mAb enhanced IL-2 production of long-term cultured, anti-CD3-stimulated T(h)1 cell lines, Moreover, anti-CD44 mAb synergized with anti-CD28 mAb in exerting this effect, A synergism of anti-CD28 and anti-CD44 mAb to co-stimulate IL-2 production was also observed in anti-CD3-triggered, freshly isolated splenic CD4(+) T cells, Blocking experiments with cyclosporin A indicated that the intracellular pathways used by the CD28 and CD44 molecules appear to be different, In contrast to the effects on the IL-2 production of T(h)1 cells, neither anti-CD44 mAb alone nor the combination of anti-CD44 with anti-CD28 were able to induce proliferation of anti-CD3-triggered T(h)1 cells, In accordance, triggering of CD44 and/or CD28 by mAb was not sufficient to reverse the previously described 'proliferative block', This term describes the unresponsiveness of T(h)1 cells against IL-2, which occurs when T(h)1 cells are triggered by anti-CD3 in the absence of co-signals. These data lead us to propose a model of T(h)1 cell activation which includes two functionally different types of co-signals: one for IL-2 production and a separate one for proliferation,