The Journal of Immunology, Vol 150, Issue 2 683-694, Copyright © 1993 by American Association of Immunologists

ARTICLES

Autoimmune thyroiditis induced in mice depleted of particular T cell subsets. Characterization of thyroiditis-inducing T cell lines and clones derived from thyroid lesions

S Sugihara, H Fujiwara and GM Shearer
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.

We have previously shown that autoimmune thyroiditis spontaneously develops in T cell-depleted (C57BL/6xC3H/He)F1 mice after adoptive transfer of syngeneic lymphoid cells that have been depleted of CD5bright T lymphocytes. This mouse model was considered to be an instructive model for Hashimoto's thyroiditis in humans, and suggested that CD5dull CD4+ autoreactive T cells are not deleted in normal lymphoid cell populations and induce thyroiditis after elimination of regulatory T cell subsets. In our study, we have established thyroid- derived T cell lines and clones by culturing thyroid-infiltrating lymphocytes with thyroid epithelial cells and syngeneic feeder cells in the presence of exogenous IL-2. Both CD4+ T cells and CD8+ T cells were identified and their CD5 expression was dull or negative. In our report, we focused on CD4+ T cells. Four CD4+ T cell lines and 19 clones were generated and characterized. CD4+ T cell clones derived from F1 hybrid (H-2b/k) mice responded to thyroid Ag in the context of not only class II MHC molecules from both parental strains (I-Ak or I- Ab), but also F1 unique MHC molecules. Thyroglobulin (Tg) was demonstrated to be a major autoantigen of the thyroid for T cell responses, and at least two epitopes of Tg were suggested to be recognized by T cell clones. An additional undefined thyroid component other than Tg was recognized by some T cell clones. Thyroid-derived T cells were all TCR-alpha beta+. Five types of V beta usage (V beta 2, 4, 8.3, 14, and an undefined V beta) were found in CD4+ T cells. Finally, the thyroid lesions could be transferred to syngeneic mice by five distinct groups of CD4+ T cell clones, which were distinguished on the basis of their Ag specificity, MHC restriction, and TCRV beta usage. The considerable heterogeneity of TCRV beta usage of thyroiditis- inducing T cell clones in this study may be attributed to the multiple patterns of their recognition of the thyroid autoantigens. These findings provide important implications for further understanding of organ-specific autoimmune processes induced by depletion of regulatory T cell subsets.

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