IL-2, IL-4, AND IFN-GAMMA GENE-EXPRESSION VERSUS SECRETION IN SUPERANTIGEN-ACTIVATED T-CELLS - DISTINCT REQUIREMENT FOR COSTIMULATORY SIGNALS THROUGH ADHESION MOLECULES

In the complete absence of APCs staphylococcal superantigens induced I L-2, IL-4, IL-5, IFN-gamma, and IL-2R gene transcripts in both highly purified human T cells and FACS sorted CD4(+) memory (CD45RA-) T cells . Secretion of IL-2, IL-4, and IFN-gamma, as well as DNA synthesis, on the other hand, required the presence of monocytes. At cytokine gene transcript level, three patterns of expression were noted after supera ntigen activation of T cells in the presence vs the absence of APC. mR NA levels for IL-2 were markedly up-regulated in the presence of monoc ytes, IL-4 and IFN-gamma transcripts increased only modestly, and IL-5 and IL-2R mRNA levels were unaffected. Blocking mAbs against LFA-1 an d LFA-3 added to staphylococcal enterotoxin B (SEB)-activated cultures of T cells and autologous monocytes, reproducibly decreased both T ce ll proliferation and genetic expression of IL-2, IL-4, IL-5, and IL-2R , although having little or no effect on IFN-gamma transcripts. Furthe r, under those conditions of blocking, secretion of IL-2 and IL-4 was dramatically decreased, whereas IFN-gamma secretion remained essential ly unchanged. In contrast, LFA-1 and LFA-3 mAbs completely abrogated I FN-gamma secretion from PHA-activated T cell-monocyte mixtures, althou gh having no inhibitory effect on T cell proliferation. These results indicate a characteristic and differential involvement of adhesion mol ecule-mediated signals in superantigen-induced T cell proliferation, d ifferential cytokine gene expression, and cytokine secretion.