IL-21 Enhances Antitumor Responses without Stimulating Proliferation of Malignant T Cells of Patients with Sézary Syndrome
Autor: | Stephen D. Hess, Alain H. Rook, Maria Wysocka, Julie H. Lin, Sarah M. Newton, Stephen K. Richardson, Jessica S. Yoon, Mariusz A. Wasik, Andrea B. Troxel, Bernice M. Benoit, Monika Kasprzycka |
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Rok vydání: | 2008 |
Předmět: |
Antigens
Differentiation T-Lymphocyte CD4-Positive T-Lymphocytes Skin Neoplasms Dipeptidyl Peptidase 4 Apoptosis Dermatology CD8-Positive T-Lymphocytes Biochemistry Interferon-gamma Interleukin 21 Immune system Antigens CD Tumor Cells Cultured Humans Sezary Syndrome Medicine Lectins C-Type RNA Messenger IL-2 receptor Antigen-presenting cell Molecular Biology business.industry Interleukins ZAP70 Cell Biology Acquired immune system Natural killer T cell Up-Regulation Killer Cells Natural Immunology Interleukin 12 Receptors Interleukin-21 K562 Cells business Cell Division |
Zdroj: | Journal of Investigative Dermatology. 128:473-480 |
ISSN: | 0022-202X |
Popis: | 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. |
Databáze: | OpenAIRE |
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