Functional analysis of T cell subsets from mice bearing the lpr gene.
The autosomal recessive lpr (lymphoproliferation) gene is responsible for a thymus-dependent massive lymphoproliferation associated with the development of lupus-like autoimmune disease. Phenotypic analysis of adult lpr/lpr lymph nodes has demonstrated accumulation of a dull Lyt-1+, Thy-1+ population that expresses neither Lyt-2 nor L3T4 antigens. With the use of a depletion method based on complement-mediated lysis with an anti-Lyt-2 monoclonal antibody (31 M) and a new anti-L3T4 monoclonal antibody (RL 172.4), we have purified the Lyt-2- L3T4- subset from lymph nodes or spleens of C57BL/6-lpr/lpr mice and determined whether they are immunologically functional in vitro. Production of neither interleukin 2 nor interferon-gamma was detected by the double-negative subset after stimulation with concanavalin A and/or phorbol myristate acetate. The frequencies of allospecific cytotoxic T lymphocyte (CTL) precursors and lectin-induced antigen-nonspecific CTL precursors were diminished to almost undetectable levels, whereas the Lyt-2+ population from lpr/lpr mice had CTL-precursor frequencies comparable with that of +/+ mice. These results show that the major cell subset of adult lpr/lpr lymph nodes or spleens is composed of lymphocytes with markedly limited potential for lymphokine production or antigenic stimulation.
D000818:Animals; D000950:Antigens, Ly; D000954:Antigens, Surface / Q000032:analysis; D002469:Cell Separation; D003208:Concanavalin A / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D005260:Female; D005434:Flow Cytometry; D005808:Genes, Recessive; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D007519:Isoantigens / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008817:Mice, Mutant Strains / Q000276:immunology*; D010641:Phenotype; D013601:T-Lymphocytes / Q000145:classification* / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000950:Antigens, Ly; D000954:Antigens, Surface; D007376:Interleukin-2; D007519:Isoantigens; D003208:Concanavalin A; D007371:Interferon-gamma