Proliferation of human T lymphocytes induced with superantigens is not dependent on costimulation by the CD28 counter-receptor B7.
Staphylococcal enterotoxins, also known as superantigens (SAg), bind class II MHC molecules on APC and upon direct cell-to-cell contact stimulate proliferation of T cells expressing appropriate V beta gene products. The T cell surface molecule CD28 binds its costimulatory counter-receptor, B7 expressed on APC, and augments IL-2 production and T cell growth. Although the role of B7 costimulation during Ag-specific responses of T cells is established, its involvement during the activation of T cells with SAg has not been examined. Using a soluble Ig C gamma 1 chimera of CTLA-4, a second receptor for B7 and a homologue of CD28, this study examines the role of B7 expressed on APC during the induction of proliferation of CD4+ T cells upon stimulation with SAg (SAg/staphylococcal enterotoxins). CTLA-4lg, which has a higher avidity for B7 than CD28, had no effect on the synthesis of IL-2 as well as proliferative responses of CD4+ T cells induced by SAg presented on allogeneic EBV-transformed B cells, and IFN-gamma-activated endothelial cells. In contrast, T cell proliferation induced by alloAg presentation by the same APC was significantly inhibited by CTLA-4lg. mAb directed at the CD11a/CD18 molecule inhibited both SAg-induced and alloAg-induced proliferation of T cells. AlloAg-primed CD4+ T cells, which expressed both class II MHC and intercellular adhesion molecule-1 but not B7, presented SAg to and induced proliferation of both resting and SAg-primed T cells. These responses were inhibited by mAb directed at CD11a/CD18 but not by CTLA-4 Rg. These results suggest that SAg-induced responses differ from those induced by alloAg in that they are not obligatorily dependent on the costimulation by B7. In contrast, adhesive interaction between CD11a/CD18 on T cells and its counter-receptor on SAg-presenting cells is necessary and probably sufficient to support SAg-induced proliferation of T cells.
Damle
N K
NK
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, WA 98121.
Klussman
K
K
Leytze
G
G
Linsley
P S
PS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology*; D015703:Antigens, CD / Q000502:physiology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D000954:Antigens, Surface / Q000502:physiology*; D018122:B7-1 Antigen; D018845:CD11 Antigens; D018821:CD18 Antigens; D018106:CD28 Antigens; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D004768:Enterotoxins / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D013211:Staphylococcus aureus / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D018122:B7-1 Antigen; D018845:CD11 Antigens; D018821:CD18 Antigens; D018106:CD28 Antigens; D004768:Enterotoxins; C031818:enterotoxin B, staphylococcal; D007371:Interferon-gamma