Induction of specific clonal anergy in human T lymphocytes by Staphylococcus aureus enterotoxins.
The exotoxins produced by certain strains of Staphylococcus aureus are able to stimulate powerful polyclonal proliferative responses and to induce nonresponsiveness by clonal deletion of T lymphocytes expressing the appropriate T-cell antigen receptor V beta gene products. This paper examines the ability of S. aureus enterotoxins to modulate the responsiveness of human CD4+ T lymphocytes with defined antigen specificity. It was observed that certain S. aureus toxins were able to activate and induce anergy in hemagglutinin-reactive T cells expressing V beta 3+ elements. After exposure to S. aureus enterotoxins A, B, and D in the absence of antigen-presenting cells, the T cells failed to respond to their natural ligand presented in an immunogenic form, despite enhanced proliferation to exogenous interleukin 2. The S. aureus toxin-induced anergy was associated with modulation of T-cell membrane receptors; down-regulation of the T-cell antigen receptor was concomitant with enhanced expression of CD2 and CD25. Interestingly, CD28 was increased only on stimulation, suggesting this protein may be differentially expressed by activated and anergic T cells. These results indicate that bacterial toxins are able to induce antigen-specific nonresponsiveness in human T cells, the application of which may be relevant in the regulation of T cells expressing a particular family of V beta gene products.
O'Hehir
R E
RE
ImmuLogic Pharmaceutical Corporation, Palo Alto, CA 94304-1103.
Lamb
J R
JR
D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D000956:Antigens, Viral / Q000276:immunology; D018801:CD2 Antigens; D018106:CD28 Antigens; D017252:CD3 Complex; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002999:Clone Cells; D015536:Down-Regulation; D004768:Enterotoxins / Q000276:immunology*; D005434:Flow Cytometry; D006389:Hemagglutinins, Viral / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D009975:Orthomyxoviridae / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D013211:Staphylococcus aureus / Q000276:immunology*; D015854:Up-Regulation
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000956:Antigens, Viral; D018801:CD2 Antigens; D018106:CD28 Antigens; D017252:CD3 Complex; D004768:Enterotoxins; D006389:Hemagglutinins, Viral; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2