title: Normal clonal expansion but impaired Fas-mediated cell death and anergy induction in interleukin-2-deficient mice.
abstract: Despite a normal development of all major lymphoid subsets, with time, interleukin-2 (IL-2)-deficient mice develop a fatal immunopathology. The disease phenotype is characterized by lymphoadenopathy, splenomegaly, T cell infiltration of various organs, overproduction of a number of cytokines and autoantibody formation. Phenotypically, CD4+ and CD8+ T cells exhibit features characteristic of antigenically experienced cells. The accumulation of cells with a memory phenotype together with the previous suggestion of an involvement of IL-2 in the termination phase of immune responses prompted us to study the fate of superantigen-reactive T cells in IL-2-deficient mice in comparison to their IL-2-producing littermates. We show that expansion in vivo of CD4+ and, to a lesser extent, CD8+ T cells reactive to the superantigens staphylococcal enterotoxin A and B (SEA and SEB) proceeds normally in the absence of IL-2, but that fewer CD4+ cells are subsequently deleted. The residual superantigen-reactive cells fail to become anergic as measured by proliferation in vitro in response to the same superantigen. T cell blasts generated in vitro from lymph node cells of IL-2-deficient mice by superantigen stimulation in the absence of exogenous IL-2 also fail to become anergic. In contrast to cells from IL-2-producing littermates, they do not exhibit Fas-induced apoptosis when cultured on anti-Fas antibody-coated plates, although Fas expression by IL-2-deficient cells is normal or even elevated compared to the IL-2-producing control cells. The data suggest that activation of T cells in the absence of IL-2 fails to generate a signal which is necessary to activate the apoptotic pathway and thus leads to an accumulation of antigen-experienced cells and the chronic inflammatory responses observed in IL-2-deficient mice.
authors.affiliation: Institute of Virology and Immunobiology, Würzburg, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Kneitz
authors.forename: T
authors.initials: T
authors.lastname: Herrmann
authors.forename: S
authors.initials: S
authors.lastname: Yonehara
authors.forename: A
authors.initials: A
authors.lastname: Schimpl
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D004768:Enterotoxins / Q000276:immunology; D007376:Interleukin-2 / Q000172:deficiency*; D051379:Mice; D018089:Superantigens / Q000276:immunology; D019014:fas Receptor / Q000276:immunology*
chemical_list: D004768:Enterotoxins; D007376:Interleukin-2; D018089:Superantigens; D019014:fas Receptor