Normal thymic selection, superantigen-induced deletion and Fas-mediated apoptosis of T cells in IL-2 receptor beta chain-deficient mice |
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Authors: | Suzuki, H Hayakawa, A Bouchard, D Nakashima, I Mak, TW |
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Affiliation: | Department of Immunology, Nagoya University, School of Medicine, Japan. |
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Abstract: | Mice lacking the IL-2 receptor beta chain (IL-2R beta) exhibit anautoimmune reaction characterized by generalized T cell activation,production of autoantibodies, myeloproliferation and severe anemia. T cellsof IL-2R beta-/- mice were examined to elucidate the mechanism responsiblefor their abnormal activation and to determine how such abnormal activationmight affect other cell lineages. Elevated levels of IgG, IgE andautoantibodies in IL-2R beta-/- mice were found to be associated withactivated CD4+ T cells which secreted elevated levels of IL-4. Thymocytesin IL-2R beta-/- mice showed normal negative and positive selectionpatterns when analyzed in transgenic mice bearing a TCR specific for HYantigen, suggesting that neither IL-2 nor IL-15 is essential for thymicselection. Peripheral T cells in IL-2R beta- deficient mice underwentnormal programmed cell death in response to staphylococcal enterotoxin Bsuperantigen, in contrast to cells from mice deficient for either IL-2 orIL-2R alpha. Activated T cells in IL- 2R beta-deficient mice expressednormal levels of Fas antigen and underwent normal apoptosis in response toinduction with anti-Fas mAb. Thus, the accumulation of activated T cells inIL-2R beta-/- mice does not appear to be derived from abnormalities ineither thymic selection or Fas-mediated apoptosis. |
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