The Journal of Immunology, Vol 151, Issue 3 1606-1613, Copyright © 1993 by American Association of Immunologists

ARTICLES

T cells involved in human autoimmune disease are resistant to tolerance induction

CM Dayan, NR Chu, M Londei, B Rapoport and M Feldmann
Immunology Unit, Kennedy Institute of Rheumatology, London, UK.

Deletion of potentially self-reactive T-cell clones during intrathymic development provides an important mechanism of preventing autoreactivity. However, some potentially damaging cells may escape this process. Recent evidence suggests that these cells may be rendered 'anergic', that is, nonresponsive to Ag, in the absence of cell death. Such a mechanism may be particularly important in maintaining tolerance to organ-specific self Ag that are not expressed in the thymus. If so, the emergence of T cells resistant to anergy induction might be expected to result in autoimmune disease. It has previously been shown that anergy can be induced in human T cells in vitro by exposure to specific target peptide or bacterial enterotoxins in the absence of Ag- presenting cells. We have recently defined the antigenic specificity of multiple T-cell clones present at the site of a human organ-specific autoimmune disease, Graves' thyroiditis (Graves disease). In the current work, thyroid-derived T cells recognizing residues 535-551 of the thyroid tissue-specific enzyme, TPO3 have been used to examine whether cells actively involved in the autoimmune process are resistant to anergy induction, as defined by anergy induction with in vitro systems. Two systems were used. First, supraimmunogenic concentrations of peptide 535-551 (up to 1 mg/ml) failed to significantly anergize these T cells in the absence of APC. In addition, the bacterial enterotoxin SED that could stimulate these T cells in the presence of APC, failed to induce anergy when APC were not present. T cells from the peripheral blood of the same individual, in contrast, were anergizable with bacterial enterotoxins, using the same protocol. These results suggest that thyroid-infiltrating autoantigen-reactive T cells are refractory to induction of anergy, and the possibility is raised that this deficiency may be of importance in the development of autoimmunity.

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