LIGATION OF CD2 PROVIDES A STRONG HELPER SIGNAL FOR THE PRODUCTION OFTHE TYPE-2 CYTOKINES INTERLEUKIN-4 AND INTERLEUKIN-5 BY MEMORY T-CELLS

In this study, we investigated the efficiency of costimulatory signali ng provided by anti-CD2 monoclonal antibodies (mAbs) for the productio n of type 1 (IL-2 and IFN-gamma) and type 2 (IL-4, IL-5, and IL-10) cy tokines by human T cells. We cultured purified human T cells (freshly isolated from blood) with immobilized anti-CD3 mAb, either alone or in combination with anti-CD28 or anti-CD2 mAbs. When compared with the s tandard costimulatory signal anti-CD28, anti-CD2 mAbs (9-1 plus 9.6) w ere shown to be more potent costimulators of IL-4 production and to ha ve similar activity for IL-5 production, but to be less potent for cos timulation of IL-2, IL-10, and IFN-gamma production, IL-4 production w as completely inhibited by cyclosporin A or by blocking IL-2 activity and its receptor. IL-4 and IL-5 were produced by CD45RO(+) T cells but not by CD45RA(+) T cells, indicating that anti-CD2 in this system cos timulated type 2 cytokine production by differentiated memory cells. I n the presence of IL-12, the cytokine profile was shifted to high IFN- gamma and IL-10 production and IL-4 and IL-5 production were slightly inhibited. Our data thus suggest that CD2 ligation plays an important role in the upregulation of Th2-like T cell activity (especially IL-4 production), but they also show that this effect is strongly modulated by IL-12, resulting in predominant IL-10 and IFN-gamma production ins tead. (C) 1997 Academic Press.