CD4+CD25+ and CD4+CD25- T cells act respectively as inducer and effector T suppressor cells in superantigen-induced tolerance.
The repeated injection of low doses of bacterial superantigens (SAg) is known to induce specific T cell unresponsiveness. We show in this study that the spleen of BALB/c mice receiving chronically, staphylococcal enterotoxin B (SEB) contains SEB-specific CD4(+) TCRBV8(+) T cells exerting an immune regulatory function on SEB-specific primary T cell responses. Suppression affects IL-2 and IFN-gamma secretion as well as proliferation of T cells. However, the suppressor cells differ from the natural CD4(+) T regulatory cells, described recently in human and mouse, because they do not express cell surface CD25. They are CD152 (CTLA-4)-negative and their regulatory activity is not associated with expression of the NF Foxp3. By contrast, after repeated SEB injection, CD4(+)CD25(+) splenocytes were heterogenous and contained both effector as well as regulatory cells. In vivo, CD4(+)CD25(-) T regulatory cells prevented SEB-induced death independently of CD4(+)CD25(+) T cells. Nevertheless, SEB-induced tolerance could not be achieved in thymectomized CD25(+) cell-depleted mice because repeated injection of SEB did not avert lethal toxic shock in these animals. Collectively, these data demonstrate that, whereas CD4(+)CD25(+) T regulatory cells are required for the induction of SAg-induced tolerance, CD4(+)CD25(-) T cells exert their regulatory activity at the maintenance stage of SAg-specific unresponsiveness.
D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D060908:CTLA-4 Antigen; D002465:Cell Movement / Q000276:immunology; D002469:Cell Separation; D017635:Clonal Anergy / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D015536:Down-Regulation / Q000276:immunology; D004334:Drug Administration Schedule; D004768:Enterotoxins / Q000008:administration & dosage* / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000276:immunology; D005260:Female; D007274:Injections, Intraperitoneal; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000008:administration & dosage* / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556707:Ctla4 protein, mouse; D004768:Enterotoxins; D018984:Epitopes, T-Lymphocyte; D015375:Receptors, Interleukin-2; D018089:Superantigens; C031818:enterotoxin B, staphylococcal