Sézary syndrome T-cell clones display T-helper 2 cytokines and express the accessory factor-1 (interferon-gamma receptor beta-chain).
Sézary 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.
Dummer
R
R
Department of Dermatology, University of Zürich Medical School, Switzerland.
Heald
P W
PW
Nestle
F O
FO
Ludwig
E
E
Laine
E
E
Hemmi
S
S
Burg
G
G
D001483:Base Sequence; D002999:Clone Cells; D016207:Cytokines / Q000378:metabolism*; D017931:DNA Primers / Q000737:chemistry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016130:Immunophenotyping; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes / Q000737:chemistry; D012333:RNA, Messenger / Q000235:genetics; D017471:Receptors, Interferon / Q000378:metabolism*; D012751:Sezary Syndrome / Q000503:physiopathology*; D018418:Th2 Cells / Q000502:physiology*; D014407:Tumor Cells, Cultured
D016207:Cytokines; D017931:DNA Primers; C086185:IFNGR2 protein, human; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D017471:Receptors, Interferon