Showe, Louise C.;
Fox, Floyd E.;
Williams, Donna;
Au, Karen;
Niu, Zhutian;
Rook, Alain H.
Depressed IL-12-Mediated Signal Transduction in T Cells from Patients with Sézary Syndrome Is Associated with the Absence of IL-12 Receptor β2 mRNA and Highly Reduced Levels of STAT4
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Media type:
E-Article
Title:
Depressed IL-12-Mediated Signal Transduction in T Cells from Patients with Sézary Syndrome Is Associated with the Absence of IL-12 Receptor β2 mRNA and Highly Reduced Levels of STAT4
Contributor:
Showe, Louise C.;
Fox, Floyd E.;
Williams, Donna;
Au, Karen;
Niu, Zhutian;
Rook, Alain H.
imprint:
The American Association of Immunologists, 1999
Published in:The Journal of Immunology
Language:
English
DOI:
10.4049/jimmunol.163.7.4073
ISSN:
0022-1767;
1550-6606
Origination:
Footnote:
Description:
<jats:title>Abstract</jats:title>
<jats:p>Sézary syndrome (SS) is the leukemic phase of cutaneous T cell lymphoma characterized by the proliferation of clonally derived CD4+ T cells that release cytokines of the Th2 T cell phenotype (IL-4, IL-5, IL-10), whereas Th1 T cell cytokines (IL-2, IFN-γ) are markedly depressed as is expression of IL-12, a pivotal cytokine for Th1 cell differentiation. Normal Th1 cells express both the β1 and β2 chains of the IL-12 receptor (IL-12R) and tyrosine phosphorylate STAT4 in response to IL-12. Th2 T cells express only the IL-12R β1 and thus do not tyrosine phosphorylate STAT4 in response to IL-12. To determine whether SS cells are Th2-like at the level of IL-12 signal transduction, we analyzed RNA from seven patients for the presence of message for the IL-12R β1 and β2 genes using RNase protection assays and assessed whether IL-12 induced tyrosine-phosphorylation of STAT4 by immunoblotting. In PBL from six of seven SS patients tested, β2 message was expressed at low to undetectable levels and its expression could not be stimulated by either IFN-α or IFN- γ, which stimulated β2 expression in control PBL. The absence of β2 expression is further supportive evidence for the Th2 lineage of SS cells. However, unlike normal Th2 cells, SS cells also showed severely reduced levels of STAT4, suggesting that they have a depressed response to any inducer of the STAT4 signal transduction pathway, including IFN-α. This is the first observation linking STAT4 gene expression with a human disease and suggests that dysregulation of STAT4 expression may be significant to the development and/or progression of SS.</jats:p>