Co-stimulation lowers the threshold for activation of naive T cells by bacterial superantigens.
Staphylococcus enterotoxins bind class II MHC molecules on antigen presenting cells (APC) and stimulate T cells expressing appropriate V beta gene products. Although the role of non-TCR associated co-stimulatory receptors during antigen-specific T cell stimulation has been clearly established, the involvement of co-stimulatory activity in T cell activation 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 enterotoxin A, staphylococcal enterotoxin B and toxic shock syndrome type 1). We demonstrate that the APC population able to activate naive T cells to IL-2 production is heterogeneous, comprising both adherent (presumably dendritic) and non-adherent (mostly B lymphocytes) cells. By stimulating naive T cells in the presence of graded doses of superantigens, we have observed that half-maximal IL-2 production was achieved at lower doses of superantigens in the presence of dendritic cells. Similarly, addition of antibodies to CD28 or B7.1-transfected cell lines increased the sensitivity of naive T cells to lower doses of superantigens. These observations indicate therefore that superantigens can be presented to naive T cells by APC displaying distinct levels of co-stimulatory activity, although with different efficacy. Thus, naive T cells are sensitive to CD28-mediated co-stimulation during superantigen-mediated responses but IL-2 production can be induced by high doses of superantigens in the presence of APC expressing weak co-stimulatory activity. These observations are compatible with the hypothesis that CD28-mediated signals participate in T cell activation by lowering T cell sensitivity to TCR ligands.
Muraille
E M
EM
Département de Biologie Moléculaire, Université Libre de Bruxelles, Rhode-St-Genèse, Belgium.
De Becker
G
G
Bakkus
M
M
Thielemans
K
K
Urbain
J
J
Moser
M
M
Leo
O
O
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001483:Base Sequence; D002460:Cell Line; D004768:Enterotoxins / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D007376:Interleukin-2 / Q000032:analysis; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D015398:Signal Transduction / Q000276:immunology*; D013154:Spleen / Q000166:cytology; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D004768:Enterotoxins; D007376:Interleukin-2; D018089:Superantigens; C026066:enterotoxin A, Staphylococcal; C031818:enterotoxin B, staphylococcal