Thyroid-specific T cells in the Wistar rat: 3. Induction of anergy by a syngeneic thyroid cell line.
Using a syngeneic Wistar rat model we have shown that the Wistar rat thyroid (WRT) cell line causes significant and specific proliferation of lymph node T cells from normal Wistar rats, and of splenic T cells from a thyroiditis prone line of BB/W rats, when cultured in the presence of irradiated feeder cells. These T cell responses were associated with a marked increase in the number of CD8+ T cells. However, using normal Wistar rat T cells which had been previously exposed to WRT cells, rested and then re-exposed to WRT cells as antigen, we consistently found that the T cell population had been rendered unreactive, or anergic, to further thyroid cell stimulation. However, if recombinant rat IL-2 was added to the cultures, then T cell responsivity was seen on re-exposure to WRT cells. The lymphopenic BB/W rat also had T cells which showed a primary T cell response to the WRT cell line accompanied by a marked increase in CD8+ T cells. In contrast to the Wistar rat T cells, the BB/W T cells retained a proliferative responsiveness to WRT cells on re-exposure although such responsiveness could also be markedly enhanced with IL-2. These data suggested that antigen-mediated inhibitory signals were induced in normal Wistar rat T cells by the syngeneic WRT cell line, independent of the presence of co-stimulatory molecules. Furthermore, the thyroiditis prone BB/W rat T cells appeared to be less responsive to such anergy induction, perhaps contributing to their susceptibility to autoimmune thyroid disease.
Kimura
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Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA.
Davies
T F
TF
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D002478:Cells, Cultured; D017635:Clonal Anergy / Q000276:immunology*; D005260:Female; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000494:pharmacology; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051381:Rats; D011913:Rats, Inbred BB; D017208:Rats, Wistar; D013154:Spleen / Q000276:immunology; D013961:Thyroid Gland / Q000276:immunology*; D013966:Thyroiditis / Q000276:immunology*
D007376:Interleukin-2