CD8 ؉ CD25 ؉ cells, which expressed high levels of Foxp3, glucocorticoid-induced tumor necrosis factor receptor (GITR), CCR8, tumor necrosis factor receptor 2 (TNFR2), and cytotoxic T-lymphocyteassociated antigen 4 (CTLA-4) mRNAs, were identified in the fibrous septa and medullary areas of human thymus. Activated CD8 ؉ CD25 ؉ thymocytes did not produce cytokines, but most of them expressed surface CTLA-4 and transforming growth factor 1 (TGF-1). Like CD4 ؉ CD25 ؉ , CD8 ؉ CD25 ؉ thymocytes suppressed the proliferation of autologous CD25-T cells via a contact-dependent mechanism. The suppressive activity of CD8 ؉ CD25 ؉ thymocytes was abrogated by a mixture of anti-CTLA-4 and anti-TGF-1 antibodies and it was mediated by their ability to inhibit the expression of the interleukin 2 receptor ␣ chain on target T cells. These results demonstrate the existence of a subset of human CD8 ؉ CD25 ؉ thymocytes sharing phenotype, functional features, and mechanism of action with CD4 ؉ CD25 ؉ T regulatory cells.
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