Lack of suppressive CD4+CD25+FOXP3+ T cells in advanced stages of primary cutaneous T-cell lymphoma.

Full Abstract

Mycosis fungoides and its leukemic variant, Sezary syndrome, are the most common primary cutaneous T-cell lymphomas (CTCLs). In an ex vivo study, we investigated the percentage, phenotype, and suppressive function of CD4+CD25+ regulatory T cells (Tregs) from peripheral blood of CTCL patients. The percentage of Tregs did not differ significantly between patients and controls. Functional assays demonstrated a dichotomy in Treg function:
in four out of 10 patients CD4+CD25+ T cells were incapable of suppressing autologous CD4+CD25- T-cell proliferation, whereas suppressive function was intact in the other six patients. Suppressive activity of Tregs inversely correlated with the peripheral blood tumor burden. T-plastin gene expression, used as a Sezary cell marker, confirmed that Sezary cells were heterogeneous for CD25 expression. Mixed lymphocyte reactions demonstrated that CD4+CD25- T cells from patients who lacked functional Tregs were susceptible to suppression by Tregs from healthy controls, and had not become suppressive themselves. Furthermore, we found reduced expression of Foxp3 in the CD4+CD25+ Tregs of these patients relative to the other six CTCL patients and controls. Our findings thus indicate a dysfunction of peripheral Tregs in certain CTCL patients, which correlates with tumor burden.

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Author information

Author/s: Tiemessen, Machteld M (MM); Mitchell, Tracey J (TJ); Hendry, Lisa (L); Whittaker, Sean J (SJ); Taams, Leonie S (LS); John, Susan (S);

Affiliation: Immunobiology Department, Division of Immunology, Infection and Inflammatory Disease, King's College London School of Medicine at Guy's, King's College and St Thomas' Hospitals, London, UK.

Grants: (Agency:Wellcome Trust)

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: The Journal of investigative dermatology (J Invest Dermatol), published in United States. (Language: eng)

Reference: 2006-Oct; vol 126 (issue 10) : pp 2217-23

Dates: Created 2006/09/19; Completed 2006/10/26; Revised 2007/08/13;

PMID: 16741512, status: MEDLINE (last retrieval date: 12/26/2008)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Aged
Antigens, CD
Antigens, Differentiation - genetics
Female
Forkhead Transcription Factors - analysis; genetics
Humans
Lymphoma, T-Cell, Cutaneous - immunology; pathology

Lymphoma, T-Cell, Cutaneous - immunology; pathology
Male
Middle Aged
Neoplasm Staging
RNA, Messenger - analysis
Skin Neoplasms - immunology; pathology
T-Lymphocytes, Regulatory - physiology

Associated Chemicals: Antigens, CD (0) ; Antigens, Differentiation (0) ; FOXP3 protein, human (0) ; Forkhead Transcription Factors (0) ; RNA, Messenger (0) ; cytotoxic T-lymphocyte antigen 4 (0)

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