Impaired AMLR in autoimmunity.
A defective AMLR and impaired production and response to Interleukin 2 (IL-2) occur as a common feature of disease in several autoimmune-susceptible strains of mice and in patients with various autoimmune and lymphoproliferative disorders. We have studied the functional significance of these abnormalities and the cellular mechanism responsible by measuring specific antigen-induced proliferation following in vivo immunization with TNP25-KLH in three autoimmune strains bearing the lpr gene. The lpr mice manifest a decreased response in this assay system. Mixing experiments, in which T cells and macrophages from lpr mice and their normal congenic partners are allowed to interact, demonstrate that the defect resides with the responding Lyt 1+ T cells and not with lpr antigen-presenting macrophages. Flow cytofluorometry analysis using monoclonal antibodies to Thy 1.2, Lyt 1 and Lyt 2 reveals an abnormal distribution of these T cells reflecting a low antigen density on the cell surface. The actual number of Lyt 1+ cells is not diminished, but the pattern is displaced. These results suggest that the decreased AMLR, decreased IL-2 production, and decreased antigen-induced proliferation are not due to deficient numbers of responding cells but rather to functional impairment.
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000941:Antigens / Q000276:immunology*; D000950:Antigens, Ly / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology*; D005260:Female; D005802:Genes, MHC Class II; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008232:Lymphoproliferative Disorders / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D013601:T-Lymphocytes / Q000276:immunology
D000941:Antigens; D000950:Antigens, Ly; D001324:Autoantigens; D007376:Interleukin-2