The selection of effector T cell phenotype by contrasuppression modulates susceptibility to autoimmune injury.
The genetic susceptibility to murine alpha TBM disease is a dominant trait that maps to H-2K. In previous studies we have shown that the critical difference between susceptible (SJL) and nonsusceptible (B10.S(8R] mice is the phenotype of the tubular Ag-specific effector T cells (TDTH). In SJL mice, these TDTH are Lyt-2+, whereas in B10.S(8R) mice the TDTH are L3T4+. These phenotypic differences have an important functional correlate: Lyt-2+ TDTH are nephritogenic, whereas L3T4+ TDTH are typically not nephritogenic. Both mouse strains have the potential to differentiate both L3T4+ and Lyt-2+ TDTH. The preferential selection of a single TDTH phenotype in each is the result of differential T cell regulation. In the present studies, we have examined the contribution of suppressor and contrasuppressor T cells in the regulation of TDTH phenotype selection. Our studies show that in both SJL and B10.(8R) mice, after exposure to Ag, a suppressor T cell subpopulation functions to inhibit the nephritogenic Lyt-2+ TDTH. In SJL, but not B10.S(8R) mice, this suppression is counterbalanced by Lyt-2+, Vicia Villosa lectin-adherent T cells. Such contrasuppressor function is mediated through a T cell-derived soluble protein (TcsF), which is Ag-binding and recognized by alpha I-JS antisera. This functional TcsF activity maps, as does susceptibility to disease, to H-2K. In the presence of genetically compatible TcsF, the TDTH phenotype in nonsusceptible mice switches to that of susceptible mice. These Lyt-2+ TDTH from nonsusceptible mice are fully capable of inducing tubulointerstitial nephritis following adoptive transfer. Our studies describe a new role for Tcs cells and augment our understanding of their etiopathogenetic role in autoimmunity.
D000818:Animals; D000950:Antigens, Ly; D001327:Autoimmune Diseases / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D002448:Cell Adhesion; D008040:Genetic Linkage; D007113:Immunity, Innate; D007674:Kidney Diseases / Q000209:etiology / Q000235:genetics / Q000276:immunology; D037102:Lectins; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D010641:Phenotype; D037121:Plant Lectins; D013045:Species Specificity; D013601:T-Lymphocytes / Q000145:classification* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000145:classification* / Q000276:immunology
D000950:Antigens, Ly; D037102:Lectins; D037121:Plant Lectins; C042242:Vicia lectins