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Sezary syndrome T-cell clones display T-helper 2 cytokines and express the
accessory factor-1 (interferon-gamma receptor beta-chain)
R Dummer, PW Heald, FO Nestle, E Ludwig, E Laine, S Hemmi and G Burg
Department of Dermatology, University of Zurich Medical School,
Switzerland.
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.
Volume 88,
Issue 4,
pp. 1383-1389,
08/15/1996
Copyright © 1996 by The American Society of Hematology
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