Regulatory CD8+ T cells control thyrotropin receptor- specific CD4+ clones in healthy subjects

One of the mechanisms ensuring immunological unresponsiveness or tolerance depends on the action of CD8(+) lymphocytes. In this paper, we report that, in healthy subjects, a subset of CD8(+)CD28(-) T cells suppresses the specific response to TSH receptor (TSHR) of CD4(+) clones. Suppression was highly specific, required cell-cell interaction, and was not mediated by cytotoxicity. Co-incubation of CD8(+) and CD4(+) clones, followed by the removal of the CD8(+) cells from the cultures before testing CD4(+) responsiveness to TSHR, demonstrated that CD4(+) cells were anergic since they showed low response to the antigen and a significant impairment of IL-2 production. In CD8-mediated anergy induction, the T-cell receptor (TCR) on both CD4(+) and CD8(+) cells seems to play a role. Our results indicate that one of the mechanisms ensuring peripheral tolerance involve CD8(+)CD28(-) cells. A disregulation in the control of autoreactive clones by this subset might be important for the onset of autoimmune thyroid diseases. (C) 2003 International Society for Preventive Oncology. Published by Elsevier Science Ltd. All rights reserved.