PT  - JOURNAL ARTICLE
AU  - Viguier, Manuelle
AU  - Lemaître, Fabrice
AU  - Verola, Olivier
AU  - Cho, Min-Sun
AU  - Gorochov, Guy
AU  - Dubertret, Louis
AU  - Bachelez, Hervé
AU  - Kourilsky, Philippe
AU  - Ferradini, Laurent
TI  - Foxp3 Expressing CD4<sup>+</sup>CD25<sup>high</sup> Regulatory T Cells Are Overrepresented in Human Metastatic Melanoma Lymph Nodes and Inhibit the Function of Infiltrating T Cells
AID  - 10.4049/jimmunol.173.2.1444
DP  - 2004 Jul 15
TA  - The Journal of Immunology
PG  - 1444--1453
VI  - 173
IP  - 2
4099  - http://www.jimmunol.org/content/173/2/1444.short
4100  - http://www.jimmunol.org/content/173/2/1444.full
SO  - J. Immunol.2004 Jul 15; 173
AB  - Dominant tolerance is mediated by regulatory T cells (Treg) that control harmful autoimmune T cells in the periphery. In this study, we investigate the implication of Treg in modulating infiltrating T lymphocytes in human metastatic melanoma. We found that CD4+CD25high T cells are overrepresented in metastatic lymph nodes (LNs) with a 2-fold increased frequency compared with both tumor-free LNs and autologous PBMCs. These cells express the Foxp3 transcription factor, display an activated phenotype, and display a polyclonal TCR Vβ chain repertoire. They inhibit in vitro the proliferation and cytokine production of infiltrating CD4+CD25− and CD8+ T cells (IL-2, IFN-γ) through a cell-contact-dependent mechanism, thus behaving as Treg. In some cases, the presence of Treg type 1/Th3-like lymphocytes could also be demonstrated. Thus, Treg are a major component of the immunosuppressive microenvironment of metastatic melanoma LNs. This could explain the poor clinical response of cancer patients under immunotherapeutic protocols, and provides a new basis for future immunotherapeutic strategies counteracting in vivo Treg to reinforce local antitumor immune responses.