PREFERENTIAL TCR V-BETA-1 GENE USAGE BY AUTOREACTIVE T-CELLS IN SPONTANEOUS AUTOIMMUNE-THYROIDITIS OF THE OBESE STRAIN OF CHICKENS

We studied T cell receptor variable beta (TCR V beta) gene usage by autoreactive T cells in spontaneous autoimmune thyroiditis (SAT) of obese strain (OS) chickens. Chicken alpha beta T cells may express either V beta 1 or V beta 2 genes, the products of which can be recognized by TCR2 and TCR3 monoclonal antibodies, respectively. Selective depletion of V beta 1(+) or V beta 2(+) T cells in OS chickens was accomplished by repeated injections of TCR2 or TCR3 antibodies into embryonic and 1-3-week-old chickens. The birds were killed at 20 days of age and their spleens and thyroid glands evaluated by immunohistochemistry. We found that V beta 1(+) T cells preferentially infiltrated OS chicken thyroid glands. Antibody treatments resulted in a 41% reduction in frequency of V beta 1(+), and a 87% reduction of the frequency of V beta 2(+) cells in the circulation, and in a profound decrease of the respective T cells in spleens and thyroid glands. Selective suppression of V beta 1(+) T cells partially inhibited SAT development in that thyroid-infiltrating cells and destruction of thyroid follicles were reduced by more than 50%. Thyroglobulin autoantibody serum levels were also reduced in V beta 1(+) T cell-depleted OS chickens, whereas selective depletion of V beta 2(+) T cells did not inhibit SAT development. These findings indicate preferential TCR V beta 1 gene usage by autoreactive T cells in SAT of OS chickens. (C) 1995 Academic Press Limited