Induction of unresponsiveness and impaired T cell expansion by staphylococcal enterotoxin B in CD28-deficient mice
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Induction of unresponsiveness and impaired T cell expansion by staphylococcal enterotoxin B in CD28-deficient mice. / Mittrücker, H W; Shahinian, A; Bouchard, D; Kündig, T M; Mak, T W.
in: J EXP MED, Jahrgang 183, Nr. 6, 01.06.1996, S. 2481-8.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Induction of unresponsiveness and impaired T cell expansion by staphylococcal enterotoxin B in CD28-deficient mice
AU - Mittrücker, H W
AU - Shahinian, A
AU - Bouchard, D
AU - Kündig, T M
AU - Mak, T W
PY - 1996/6/1
Y1 - 1996/6/1
N2 - 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.
AB - 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.
KW - Animals
KW - Antigens, CD28
KW - Cells, Cultured
KW - Crosses, Genetic
KW - Enterotoxins
KW - Flow Cytometry
KW - H-2 Antigens
KW - Immunity, Innate
KW - Immunophenotyping
KW - Interleukin-2
KW - Kinetics
KW - Lymph Nodes
KW - Lymphocyte Activation
KW - Mice
KW - Mice, Inbred BALB C
KW - Mice, Knockout
KW - Shock, Septic
KW - Staphylococcus aureus
KW - Superantigens
KW - T-Lymphocytes
KW - Time Factors
KW - Tumor Necrosis Factor-alpha
M3 - SCORING: Journal article
C2 - 8676068
VL - 183
SP - 2481
EP - 2488
JO - J EXP MED
JF - J EXP MED
SN - 0022-1007
IS - 6
ER -
