CO-STIMULATION LOWERS THE THRESHOLD FOR ACTIVATION OF NAIVE T-CELLS BY BACTERIAL SUPERANTIGENS

Staphylococcus enterotoxins bind class II MHC molecules on antigen pre senting cells (APC) and stimulate T cells expressing appropriate V-bet a gene products. Although the role of non-TCR associated co-stimulator y receptors during antigen-specific T cell stimulation has been clearl y established, the involvement of co-stimulatory activity in T cell ac tivation by superantigens has been the matter of controversy. In this report, we examine the role of co-stimulation provided by selected APC populations in the response to bacterial exotoxins (staphylococcal en terotoxin A, staphylococcal enterotoxin B and toxic shock syndrome typ e 1). We demonstrate that the APC population able to activate naive T cells to IL-2 production is heterogeneous, comprising both adherent (p resumably dendritic) and non-adherent (mostly B lymphocytes) cells. By stimulating naive T cells in the presence of graded doses of superant igens, we have observed that half-maximal IL-2 production was achieved at lower doses of superantigens in the presence of dendritic cells. S imilarly, addition of antibodies to CD28 or B7.1-transfected cell line s increased the sensitivity of naive T cells to lower doses of superan tigens. These observations indicate therefore that superantigens can b e presented to naive T cells by APC displaying distinct levels of co-s timulatory activity, although with different efficacy. Thus, naive T c ells are sensitive to CD28-mediated co-stimulation during superantigen -mediated responses but IL-2 production can be induced by high doses o f superantigens in the presence of APC expressing weak co-stimulatory activity. These observations are compatible with the hypothesis that C D28-mediated signals participate in T cell activation by lowering T ce ll sensitivity to TCR ligands.