Lack of suppressive CD4+CD25+FOXP3+ T cells in advanced stages of primary cutaneous T-cell lymphoma.
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.
Tiemessen
Machteld M
MM
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.
Mitchell
Tracey J
TJ
Hendry
Lisa
L
Whittaker
Sean J
SJ
Taams
Leonie S
LS
John
Susan
S
D000368:Aged; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics; D060908:CTLA-4 Antigen; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis* / Q000235:genetics; D006801:Humans; D016410:Lymphoma, T-Cell, Cutaneous / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000032:analysis; D012878:Skin Neoplasms / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger