Normal thymic selection, superantigen-induced deletion and Fas-mediated apoptosis of T cells in IL-2 receptor beta chain-deficient mice.
Mice lacking the IL-2 receptor beta chain (IL-2R beta) exhibit an autoimmune reaction characterized by generalized T cell activation, production of autoantibodies, myeloproliferation and severe anemia. T cells of IL-2R beta-/- mice were examined to elucidate the mechanism responsible for their abnormal activation and to determine how such abnormal activation might affect other cell lineages. Elevated levels of IgG, IgE and autoantibodies in IL-2R beta-/- mice were found to be associated with activated CD4+ T cells which secreted elevated levels of IL-4. Thymocytes in IL-2R beta-/- mice showed normal negative and positive selection patterns when analyzed in transgenic mice bearing a TCR specific for HY antigen, suggesting that neither IL-2 nor IL-15 is essential for thymic selection. Peripheral T cells in IL-2R beta-deficient mice underwent normal programmed cell death in response to staphylococcal enterotoxin B superantigen, in contrast to cells from mice deficient for either IL-2 or IL-2R alpha. Activated T cells in IL-2R beta-deficient mice expressed normal levels of Fas antigen and underwent normal apoptosis in response to induction with anti-Fas mAb. Thus, the accumulation of activated T cells in IL-2R beta-/- mice does not appear to be derived from abnormalities in either thymic selection or Fas-mediated apoptosis.
Suzuki
H
H
Department of Immunology, Nagoya University, School of Medicine, Japan.
Hayakawa
A
A
Bouchard
D
D
Nakashima
I
I
Mak
T W
TW
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D016827:CD8 Antigens / Q000235:genetics; D017637:Clonal Deletion / Q000235:genetics*; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D016654:Genes, RAG-1; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D015375:Receptors, Interleukin-2 / Q000172:deficiency* / Q000235:genetics*; D018089:Superantigens / Q000494:pharmacology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*; D019014:fas Receptor / Q000096:biosynthesis / Q000502:physiology*
D016827:CD8 Antigens; D016207:Cytokines; D015375:Receptors, Interleukin-2; D018089:Superantigens; D019014:fas Receptor; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)