Thyroglobulin-reactive T lymphocytes in thyroiditis-prone BB/Wor rats.
Autoimmune lymphocytic thyroiditis (LT) is a common cause of primary hypothyroidism. Autoreactive T lymphocytes are clearly associated with this disorder, but their pathogenic role in spontaneously occurring LT remains to be established. In the present study, thyroglobulin-reactive T lymphocytes were cultured from young, unprimed LT-prone BB/Wor rats before the age of spontaneously-occurring LT. Although similar investigations have been conducted in animal models for experimental autoimmune thyroiditis (EAT), this study is unique because it examines a mammalian model for spontaneous LT. Splenic T lymphocytes were isolated from unprimed 30 to 45-day-old Fisher and LT-prone BB/Wor rats before the onset of LT, then tested for activation by normal (NL), iodine-poor (LI), and iodine-rich (HI) rat thyroglobulin (Tg) in bulk proliferation assay. BB/Wor rat lymphocytes were activated by all three Tg preparations, but Fisher lymphocytes were unresponsive (BB/Wor vs Fisher; p < 0.0001, Student's t-test). There was no difference between BB/Wor rat responses to the three preparations (p > 0.05, ANOVA). Based on these results, we conclude that Tg-responsive T lymphocytes can be cultured from young, unprimed LT-prone BB/Wor rats. Isolating such lymphocytes before the onset of histologically demonstrable LT strengthens the argument that antigen-specific T cells have a pathogenic role in the development of spontaneous autoimmune thyroid disease. The fact that these lymphocytes recognized normal, iodine-rich and iodine poor preparations of rat Tg equally well suggest that unlike the EAT model, spontaneously-occurring Tg-reactive T cells are not influenced by thyroglobulin's iodine content.
Allen
E M
EM
Medical Service, Baltimore Veterans Administration Medical Center, Maryland, USA.
Thupari
J N
JN
D000818:Animals; D001323:Autoantibodies / Q000494:pharmacology; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology*; D013954:Thyroglobulin / Q000276:immunology* / Q000494:pharmacology; D013967:Thyroiditis, Autoimmune / Q000276:immunology*
D001323:Autoantibodies; D007376:Interleukin-2; D003208:Concanavalin A; D013954:Thyroglobulin