Defective LN cell proliferative response to Sm antigen in mice bearing the lpr gene.
Several normal and lpr/lpr congenic mouse strains were immunized with an autoantigen (Sm) and a conventional antigen (PPD) and tested for their respective in vitro proliferative responses. All normal strains of mice demonstrated a brisk proliferative response to Sm and PPD on days 3 and 5 of culture. Two month old mice bearing the lpr gene demonstrated a proliferative response to the two antigens only on day 3, while by day 5 of culture, the proliferative response was markedly diminished. Mixing experiments between +/+ and lpr/lpr Sm primed lymph node cells ruled out the influence of a suppressor cell within the lpr/lpr population at day 5. The inability to sustain an in vitro proliferative response to antigen in young lpr/lpr mice was not due to an overall T cell defect nor to in vitro cell death since Con A stimulation and viability were the same in cultures containing lpr/lpr and +/+ LN, cells, respectively. The primary defect may be partly attributed to a defect in interleukin-2 (IL-2) production and response. By day 5 of culture, lpr/lpr supernatants contained much lower levels of IL-2 activity compared to supernatants from +/+ cultures. The addition of exogenous IL-2 was only moderately successful in improving the response falling far below that seen when IL-2 was added to +/+ cultures. This study demonstrates a decrease in autoantigen-induced T cell proliferation in mice that spontaneously produce autoantibodies to that antigen.
D000818:Animals; D000941:Antigens / Q000276:immunology*; D001323:Autoantibodies / Q000096:biosynthesis*; D001324:Autoantigens / Q000276:immunology*; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology*; D008213:Lymphocyte Activation; D008232:Lymphoproliferative Disorders / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D017411:Ribonucleoproteins, Small Nuclear; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D055517:snRNP Core Proteins
D000941:Antigens; D001323:Autoantibodies; D001324:Autoantigens; D007376:Interleukin-2; D017411:Ribonucleoproteins, Small Nuclear; D055517:snRNP Core Proteins