Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.
Sezary syndrome T-cell clones display T-helper 2 cytokines and express the accessory factor-1 (interferon-gamma receptor beta-chain).
Blood. 1996 Aug 15;88(4):1383-9. Unique Identifier : AIDSLINE MED/96329572 Dummer R; Heald PW; Nestle FO; Ludwig E; Laine E; Hemmi S; Burg G; Department of Dermatology, University of Zurich Medical School,; Switzerland.
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.
Keywords: Base Sequence Clone Cells Cytokines/*METABOLISM DNA Primers/CHEMISTRY Gene Expression Regulation, Neoplastic Human Immunophenotyping Molecular Sequence Data Oligonucleotide Probes/CHEMISTRY Receptors, Interferon/*METABOLISM RNA, Messenger/GENETICS Sezary Syndrome/*PHYSIOPATHOLOGY Support, Non-U.S. Gov't Th2 Cells/*PHYSIOLOGY Tumor Cells, Cultured JOURNAL ARTICLE 961130
M96B1871
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Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.
