Activation of MHC-restricted rat T cells by cloned syngeneic thyrocytes.
We have previously demonstrated that rat thyrocytes express MHC class II Ag (RT1.B&D) in response to IFN-gamma. To determine whether MHC class II-positive thyrocytes can be recognized by MHC-restricted T cells, we used our clone of rat thyroid cells (1B-6) derived from the Fisher rat thyroid cell line (FRTL-5) and known to express MHC class II Ag in response to recombinant rat IFN-gamma. CD4+ and CD8+ normal syngeneic Fisher rat spleen T cells were selected by flow cytometry and averaged greater than 96% purity. We demonstrated that irradiated MHC class II-positive but not class II-negative 1B-6 thyrocytes stimulated CD4+ T cells in a primary sensitization reaction over 4 days. In contrast, CD8+ T cells had no response in similar experiments. This stimulation of CD4+ T cells was dose dependent for 1B-6 thyrocytes and was abrogated by anti-rat MHC class II mAb (MRC OX-6). Autoreactive (Fisher) and alloreactive (Buffalo) T cell lines and isolated CD4+ T cells derived from these lines, which were developed against Fisher rat spleen cells, similarly recognized MHC class II Ag expressed on 1B-6 cells but had no detectable response to 1B-6 MHC class II-negative thyrocytes or MHC class II-positive human thyroid cells. The CD4+ T cell recognition of 1B-6 cells via MHC class II Ag supports our previous data with autologous human thyroid T cell co-cultures and is indicative of an autospecific role for thyrocytes in the development of autoimmune thyroiditis.
D000818:Animals; D000943:Antigens, Differentiation; D000961:Antilymphocyte Serum / Q000494:pharmacology; D002460:Cell Line; D002999:Clone Cells / Q000145:classification / Q000276:immunology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000276:immunology; D007074:Immunoglobulin G / Q000502:physiology; D018828:Immunoglobulins, Thyroid-Stimulating; D007959:Lymphocyte Culture Test, Mixed; D010641:Phenotype; D051381:Rats; D011915:Rats, Inbred BUF; D011916:Rats, Inbred F344; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology*; D013961:Thyroid Gland / Q000166:cytology* / Q000276:immunology
D000943:Antigens, Differentiation; D000961:Antilymphocyte Serum; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D018828:Immunoglobulins, Thyroid-Stimulating