Delineation of two defects responsible for T-cell hyporesponsiveness to concanavalin A in MRL congenic mice.
MRL-lpr mice and their congenic counterparts MRL-+ spontaneously develop an autoimmune disease that resembles systemic lupus erythematosus in humans. The two strains, although congenic, differ by a considerable number of disease parameters, reflecting the expression of the lpr autosomal recessive gene. One paradox that has developed out of the work utilizing the congenic mice is that the gene responsible for lymphoproliferation also appears to be responsible for the inability of T cells to respond to proliferative signals in vitro. In this paper we investigated a possible lpr gene-encoded macrophage defect in these mice. It was found, however, that both the MRL-+ and MRL-lpr mice failed to divide in response to Con A, the lack of division correlating with an inability to secrete the growth promoter interleukin-2. In MRL-+ mice and young MRL-lpr mice this non-responsiveness was corrected by the addition of normal CBA PEC. The defect could not be explained by a failure of MRL-+ or MRL-lpr peritoneal exudate cells to quantitatively or qualitatively provide a source of interleukin-1 to Con A-activated T cells or by the possibility that the peritoneal exudate cells were blocked in their function by the presence of sera-derived autoantibodies and/or immune complexes on their membranes. We postulate that the inability of T cells to proliferate in MRL congenic mice can be explained by two defects: the failure of antigen-presenting cells in MRL-+ and MRL-lpr to provide the necessary signals to immunocompetent T cells, this defect not being associated with the lpr gene, and the lpr gene controlled outgrowth of a unique T-cell population that cannot respond in our assay system.
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology*; D005802:Genes, MHC Class II; D007375:Interleukin-1 / Q000276:immunology; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D008938:Mitosis; D013601:T-Lymphocytes / Q000276:immunology*
D007375:Interleukin-1; D003208:Concanavalin A