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J Invest Dermatol ; 128(2): 473-80, 2008 Feb.
Article in English | MEDLINE | ID: mdl-17713571

ABSTRACT

IL-21, a common gamma-chain cytokine secreted by activated CD4+ T cells, influences both humoral and cell-mediated immune responses through the regulation of T, B, dendritic, and natural killer (NK) cells. Sézary syndrome is an advanced form of cutaneous T-cell lymphoma, a clonally derived malignancy of CD4+ T cells that is characterized by profound defects in host cellular immune function. As a modulator of both innate and adaptive immune responses, IL-21 could play an important role in augmenting cell-mediated immunity in these patients. Normal donor and Sézary syndrome patient peripheral blood mononuclear cells were cultured with IL-21 and tested for CD8+ T- and NK-cell activation, NK-cell cytotoxicity, and tumor cell proliferation and apoptosis. IL-21 resulted in a modest increase in CD8+ T- and NK-cell activation, associated with a marked increase in cytolytic activity against both K562 and malignant CD4+ T-cell targets. Although IL-21 failed to demonstrate pro-apoptotic effects on the malignant CD4+ T cells, it is noteworthy that it had no demonstrable proliferative effects on these cells. Thus, IL-21 may play an important role in enhancing the host immune response of Sézary syndrome patients through the increased cytolytic activity of T and NK cells.


Subject(s)
Interleukins/immunology , Sezary Syndrome/immunology , Sezary Syndrome/pathology , Skin Neoplasms/immunology , Skin Neoplasms/pathology , Antigens, CD/metabolism , Antigens, Differentiation, T-Lymphocyte/metabolism , Apoptosis/immunology , CD4-Positive T-Lymphocytes/metabolism , CD4-Positive T-Lymphocytes/pathology , CD8-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/pathology , Cell Division/drug effects , Cell Division/immunology , Dipeptidyl Peptidase 4/metabolism , Humans , Interferon-gamma/metabolism , Interleukins/pharmacology , K562 Cells , Killer Cells, Natural/metabolism , Killer Cells, Natural/pathology , Lectins, C-Type , RNA, Messenger/metabolism , Receptors, Interleukin-21/genetics , Tumor Cells, Cultured , Up-Regulation/immunology
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