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Prepublished online as a Blood First Edition Paper on July 31, 2003; DOI 10.1182/blood-2003-04-1320.

Submitted April 28, 2003
Accepted July 22, 2003
Human CD8+CD25+ thymocytes sharing phenotypic and functional features with CD4+CD25+ regulatory thymocytes
Lorenzo Cosmi, Francesco Liotta, Elena Lazzeri, Michela Francalanci, Roberta Angeli, Benedetta Mazzinghi, Veronica Santarlasci, Roberto Manetti, Vittorio Vanini, Paola Romagnani, Enrico Maggi, Sergio Romagnani, and Francesco Annunziato*
Department of Internal Medicine, University of Florence, Florence, Italy
Department of Pathophysiology, University of Florence, Florence, Italy
Apuanic Pediatric Hospital, Massa Carrara, Italy
* Corresponding author; email: f.annunziato{at}dmi.unifi.it.
CD8+CD25+ cells, which expressed high levels of Foxp3, GITR, CCR8, TNFR2, and 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 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- 1 antibodies and it was mediated by their ability to inhibit the expression of the IL-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+ Treg cells.

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