Analysis of T cell function in autoimmune murine strains. Defects in production and responsiveness to interleukin 2.

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Abstract
The production and consumption of T cell growth factor, more recently termed interleukin 2 (IL-2), and some cell-mediated immune functions were studied in murine strains [MRL, BXSB, NZB, and (NZB .times. NZW)F1] manifesting systemic lupus erythematosus (SLE)-like syndromes. Young (4-6 wk) or old (4-8 mo.) autoimmune or normal mice were studied and compared with regard to the following T cell functions in vitro after stimulation with concanavalin A (Con A): mitogenic response; IL-2 levels in culture supernates; the ability to respond to and adsorb IL-2. Proliferative activity in the allogeneic mixed leukocyte culture and frequency of alloreactive cytotoxic T lymphocyte precursors (CTLp) were analyzed in some of these strains. Reduced Con A-induced mitogenic responses and IL-2 production appeared at 3-6 wk of age in the early, severe SLE developing strains MRL/Mp-lpr/lpr (MRL/l) and male BXSB and progressed thereafter. Similar defects appeared at a later stage in MRL/MP-+/+ and (NZB .times. NZW)F1 hybrid mice, which develop late disease. Detailed analysis of cells from the enlarged lymph nodes and spleens of older MRL/l mice demonstrated the following: such cells responded poorly to Con A or allogeneic stimulator cells, even in the presence of exogenous IL-2; did not suppress IL-2 production by normal spleen cells; were relatively incapable of adsorbing or inactivating IL-2; and had a markedly reduced anti-H-2b CTLp frequency in the mesenteric lymph nodes but a normal one in spleen. The proliferating Thy-1.2+, Lyt-1+ T cells in MRL/l mice are evidently defective in their responses to mitogenic stimuli, in IL-2 production and in expression of acceptor sites for IL-2. The relevance of these defects to the MRL/l disease and to the role of IL-2 in autoimmunity in general remains to be determined.

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