T cell tolerance to self antigens in New Zealand hybrid mice with lupus-like disease.
We determined if self-reactive T cells are able to escape thymic tolerance in autoimmune New Zealand mice. T cells utilizing V beta 17a and V beta 11 encoded receptors have been shown to be clonally eliminated in nonautoimmune mice expressing I-E because of their potential self-reactivity. Similarly, V beta 8.1+ and V beta 6+ T cells are tolerized in the thymus of nonautoimmune mice that express Mls-1a. These T cell subsets were quantitated in the lymph nodes and spleens of (NZB x NZW)F1 and (NZB x SWR)F1 mice. In young mice from both autoimmune strains, deletion was similar to that observed in control animals matched for I-Ed and Mls-1a expression. Furthermore, older female autoimmune mice with elevated levels of IgG antinuclear antibodies and severe lupus-like renal disease did not demonstrate evidence of a global tolerance defect. We also found that the levels of residual V beta 17a+ cells in MHC-matched control F1 strains were further reduced by up to 80% in autoimmune (NZB x SWR)F1 mice. The greater in vivo elimination corresponded to an enhanced ability of NZB spleen cells, compared with other H-2d spleen cells, to stimulate V beta 17a+ hybridomas in vitro. The increased stimulation in culture could not be attributed to quantitative differences in I-E Ag expression. The results suggest that autoreactive T cells have been eliminated in these autoimmune mice by normal mechanisms of self-tolerance. Furthermore, the data demonstrate the existence of an NZB minor locus not present in other H-2d strains that influences T cell repertoire and enhances stimulation of T cells potentially reactive to self class II MHC Ag.
Kotzin
B L
BL
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
Kappler
J W
JW
Marrack
P C
PC
Herron
L R
LR
D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D003433:Crosses, Genetic; D005260:Female; D006825:Hybridomas / Q000276:immunology; D007108:Immune Tolerance; D007135:Immunoglobulin Variable Region / Q000235:genetics; D008181:Lupus Nephritis / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008814:Mice, Inbred NZB; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D013045:Species Specificity; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology*
D001324:Autoantigens; D007135:Immunoglobulin Variable Region; D011948:Receptors, Antigen, T-Cell