ICAM-1 COSTIMULATION INDUCES IL-2 BUT INHIBITS IL-10 PRODUCTION IN SUPERANTIGEN-ACTIVATED HUMAN CD4(-CELLS() T)

We have previously reported that costimulatory pathways including B7-C D28 and lymphocyte function-associated antigen-3 (LFA-3)-CD2 shape dis tinct activation profiles in human CD4(+) T cells. We now show that su perantigen (SAg), in combination with intracellular adhesion molecule- 1 (ICAM-1) costimulation drives a proliferative response accompanied b y high levels of interleukin-2 (IL-2) and moderate levels of interfero n-gamma (IFN-gamma) and tumour necrosis factor (TNF). This response pr ofile differs from that observed in B7 or LFA-3 costimulated T cells b ecause our previous results showed that B7-CD28 costimulation was acco mpanied by high levels of IL-2, IFN-gamma and TNF, whereas LFA-3 was a potent inducer of IFN-gamma and TNF, but had little influence on IL-2 production. The ICAM-1-induced IL-2 production could efficiently be a brogated with monoclonal antibody (mAb) against ICAM-1 or LFA-1, showi ng that the activation is dependent of a functional ICAM-1-LFA-1 pathw ay. SAg-induced IL-2, IFN-gamma and TNF were detected in both CD4+ and CD8+ T cells, whereas production of IL-10 was restricted to CD4+ T ce lls. A major finding in the present study was that ICAM-1 costimulatio n strongly inhibits IL-10 production in CD4+ T cells. Our data demonst rate that ICAM-1 costimulation is sufficient to induce large amounts o f IL-2. The presence of ICAM-1 results in suppression of IL-10 product ion in T helper (Th) cells, which may favour the development of Th1 an d not Th2 T cells.