Normal clonal expansion but impaired Fasmediated 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 superantigenreactive 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.