Sezary syndrome T-cell clones display T-helper 2 cytokines and express the accessory factor-1 (interferon-gamma receptor beta-chain)

Abstract

Sezary syndrome (SS) is a leukemic variant of low-grade cutaneous T- cell lymphomas (CTCLs). The clonal T cells in this lymphoproliferative disorder are poorly characterized. Using antibodies against the variable region of the T-cell receptor (TCR V alpha/beta), we identified four predominant T-cell clones (two V beta 8+ clones, one V beta 5.1+, and one V alpha 2(a)+) in peripheral blood mononuclear cells (PBMC) of SS patients. Their phenotype was CD3+, CD4+, CD5+, CD45RO+. Clonal T cells were purified, and cytokine transcription and secretion was analyzed by reverse transcriptase-polymerase chain reaction (RT- PCR) followed by hybridization with biotinylated probes and enzyme- linked immunosorbent assays (ELISAs). The interleukin-10 (IL-10) PCR product was cloned and sequenced and found to be identical to the published cDNA sequence. The presence of accessory factor-1 (AF-1, or interferon-gamma [IFN-gamma] receptor beta-chain) encoding mRNA was assessed by RT-PCR and immunostaining using serum of rabbits immunized with the extracellular domain of a recombinant human AF-1 protein followed by APAAP staining. Clonal T cells transcribe and secrete mainly T-helper 2 cytokines (IL-10, -5, and -13). mRNA from purified SS clones but not mRNA from SS total PBMC was positive for AF-1 in an agarose gel and/or after hybridization. AF-1 transcription was associated with membrane-bound immunoreactivity for AF-1 in SS clones. SS-derived T-cell clones display T-helper 2 cytokines. This weakens cell-mediated immunosurveillance, and explains the clinical and immunologic abnormalities in SS patients. The T-helper 2 cytokine spectrum of all clones investigated is associated with overexpression of AF-1. This suggests that AF-1 is a potential marker for these clones (and eventually other T-helper 2 lymphocytes) and might represent a target for treatment of the disease.