Induction of unresponsiveness and impaired T cell expansion by staphylococcal enterotoxin B in CD28-deficient mice.
We used CD28-deficient mice to analyze the importance of CD28 costimulation for the response against Staphylococcal enterotoxin B (SEB) in vivo. CD28 was necessary for the strong expansion of V beta 8+ T cells, but not for deletion. The lack of expansion was not due to a failure of SEB to activate V beta 8+ T cells, as V beta 8+ T cells from both CD28-/- and CD28+/+ mice showed similar phenotypic changes within the first 24 h after SEB injection and cell cycle analysis showed that an equal percentage of V beta 8+ T cells started to proliferate. However, the phenotype and the state of proliferation of V beta 8+ T cells was different at later time points. Furthermore, in CD28-/- mice injection with SEB led to rapid induction of unresponsiveness in SEB responsive T cells, indicated by a drastic reduction of proliferation after secondary SEB stimulation in vitro. Unresponsiveness could also be demonstrated in vivo, as CD28-/- mice produced only marginal amounts of TNF alpha after rechallenge with SEB. In addition CD28-/- mice were protected against a lethal toxic shock induced by a second injection with SEB. Our results indicate that CD28 costimulation is crucial for the T cell-mediated toxicity of SEB and demonstrate that T cell stimulation in the absence of CD28 costimulation induces unresponsiveness in vivo.
Mittrücker
H W
HW
Department of Immunology and Biophysics, Ontario Cancer Institute, University of Toronto, Ontario, Canada.
Shahinian
A
A
Bouchard
D
D
Kündig
T M
TM
Mak
T W
TW
D000818:Animals; D018106:CD28 Antigens / Q000235:genetics*; D002478:Cells, Cultured; D003433:Crosses, Genetic; D004768:Enterotoxins / Q000494:pharmacology* / Q000633:toxicity; D005434:Flow Cytometry; D006183:H-2 Antigens / Q000096:biosynthesis; D007113:Immunity, Innate; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000494:pharmacology; D007700:Kinetics; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D012772:Shock, Septic / Q000276:immunology; D013211:Staphylococcus aureus; D018089:Superantigens / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D018106:CD28 Antigens; D004768:Enterotoxins; D006183:H-2 Antigens; D007376:Interleukin-2; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; C031818:enterotoxin B, staphylococcal