Murine interstitial nephritis. III. The selection of phenotypic (Lyt and L3T4) and idiotypic (RE-Id) T cell preferences by genes in Igh-1 and H-2K characterizes the cell-mediated potential for disease expression: susceptible mice provide a unique effector T cell repertoire in response to tubular antigen.
The effector T cell repertoire in experimental interstitial nephritis was examined in a variety of susceptible and nonsusceptible mice. We observed that L3T4+ effector T cells in disease-susceptible mice disappear soon after immunization in preference to the emergence of Lyt-2+ effector cells. These latter cells respond with delayed-type hypersensitivity to tubular antigen in the context of H-2K. Such cells also express idiotypes (RE-Id) shared with kidney-bound alpha TBM-Ab that are regulated by an interactional effect of genes in Igh-1 and H-2K. These Lyt-2+ effector cells can be removed from renal infiltrates, and the transfer of similar cells under the renal capsule of naive mice results, within 5 days, in local interstitial nephritis. Nonsusceptible mice, however, not having these immune response genes, produce either L3T4+, Lyt-1+, RE-Id- effector T cells, which only respond to tubular antigen in the context of I-A, or Lyt-2+, RE-Id- T cells, which may lack very fine specificity. These findings suggest that susceptible mice carry a unique set of immune response genes that promote a T cell selection process that operates after induction, during the differentiation and development of disease-producing effector T cells.
Neilson
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McCafferty
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Mann
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Michaud
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Clayman
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D000818:Animals; D000941:Antigens / Q000276:immunology*; D000950:Antigens, Ly / Q000235:genetics; D000954:Antigens, Surface / Q000235:genetics; D004198:Disease Susceptibility; D000939:Epitopes / Q000276:immunology; D005802:Genes, MHC Class II; D006183:H-2 Antigens / Q000235:genetics; D064532:Histocompatibility Antigen H-2D; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007111:Immunity, Cellular; D007116:Immunization, Passive; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007130:Immunoglobulin Idiotypes / Q000235:genetics / Q000276:immunology; D007684:Kidney Tubules / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009395:Nephritis, Interstitial / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D010641:Phenotype; D011817:Rabbits; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology* / Q000473:pathology
D000941:Antigens; D000950:Antigens, Ly; D000954:Antigens, Surface; D000939:Epitopes; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D007143:Immunoglobulin Heavy Chains; D007130:Immunoglobulin Idiotypes; D016169:Lymphocyte Function-Associated Antigen-1; C035812:renal tubular antigen