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© Research
Publication : Journal of immunology (Baltimore, Md. : 1950)

Foxp3 expressing CD4+CD25(high) regulatory T cells are overrepresented in human metastatic melanoma lymph nodes and inhibit the function of infiltrating T cells

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Journal of immunology (Baltimore, Md. : 1950) - 15 Jul 2004

Viguier M, Lemaître F, Verola O, Cho MS, Gorochov G, Dubertret L, Bachelez H, Kourilsky P, Ferradini L

Link to Pubmed [PMID] – 15240741

J. Immunol. 2004 Jul;173(2):1444-53

Dominant tolerance is mediated by regulatory T cells (T(reg)) that control harmful autoimmune T cells in the periphery. In this study, we investigate the implication of T(reg) in modulating infiltrating T lymphocytes in human metastatic melanoma. We found that CD4(+)CD25(high) 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 Vbeta chain repertoire. They inhibit in vitro the proliferation and cytokine production of infiltrating CD4(+)CD25(-) and CD8(+) T cells (IL-2, IFN-gamma) through a cell-contact-dependent mechanism, thus behaving as T(reg). In some cases, the presence of T(reg) type 1/Th3-like lymphocytes could also be demonstrated. Thus, T(reg) 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 T(reg) to reinforce local antitumor immune responses.

http://www.ncbi.nlm.nih.gov/pubmed/15240741