Human CD8+CD25+ thymocytes share phenotypic and functional features with CD4+CD25+ re latory thyrnocytes

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-lymphocyte-associated antigen 4 (CTLA-4) mRhAs, were identified in the fibrous septa and medullary areas of human thymus. Activated CD8(+)CD25(+) thymocytes did not produce cytokines, but most of them ex-pressed surface CTLA-4 and transforming growth factor beta1 (TGF-beta1). 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-beta1 antibodies and it was mediated by their ability to inhibit the expression of the interleukin 2 receptor alpha 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. (C) 2003 by The American Society of Hematology.