Autoimmune CD4+ T cells interfere with immune tolerance to a thymic-independent antigen.
The ability of autoimmune T cell subsets to interfere with tolerization of B cells can be studied by using thymic-independent Ag. We have defined an abnormality within the CD4+ T cell compartment in young NZB and MRL-lpr/lpr mice by studying tolerance of spleen and B cells to the thymic independent Ag, fluorescein-Brucella abortus. Tolerization of spleen cells is defective in MRL-lpr/lpr mice, but not MRL-+/+ or C3H.lpr mice, suggesting that the defect requires both the autosomal MRL background and the lpr gene to be present. T enriched cells from NZB mice and from MRL-lpr/lpr mice (but not MRL-+/+ or C3H.lpr mice) reverse tolerance in spleen cells from [NZB X DBA/2]F1 and C3H/HeJ mice, respectively. This interference is removed by treatment with anti-CD4 antibody and C. Supernatants from cultured T cells of NZB and MRL-lpr/lpr mice also prevent tolerance in spleen cells of [NZB X DBA/2]F1 and MRL-+/+ mice, respectively, unless CD4+ cells are removed prior to T cell culture. Removal of T cells from NZB and MRL-lpr/lpr spleen cells allows normal tolerization of B cells, which is abrogated by the addition of syngeneic T cells or cultured T cell supernatants. This effect also depends on the presence of CD4+ T cells. These studies show that in MRL-lpr/lpr mice, through interaction of the lpr and MRL background genes in a T cell subset, and in NZB mice, CD4+ T cells interfere with B cell tolerance to a thymic-independent Ag.
Miller
M L
ML
Department of Pediatrics, University of Texas Health Science Center, San Antonio 78284.
Chacko
J A
JA
D000818:Animals; D000943:Antigens, Differentiation; D000955:Antigens, T-Independent / Q000276:immunology*; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D002004:Brucella Vaccine / Q000276:immunology; D005260:Female; D005452:Fluoresceins; D006241:Haptens / Q000276:immunology*; D006433:Hemocyanins / Q000276:immunology; D006462:Hemolytic Plaque Technique; D007108:Immune Tolerance; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D008814:Mice, Inbred NZB; D010641:Phenotype; D013045:Species Specificity; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology*
D000943:Antigens, Differentiation; D000955:Antigens, T-Independent; D002004:Brucella Vaccine; D005452:Fluoresceins; D006241:Haptens; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin