IL-21 enhances antitumor responses without stimulating proliferation of malignant T cells of patients with Sézary syndrome.
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.
Yoon
Jessica S
JS
Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Newton
Sarah M
SM
Wysocka
Maria
M
Troxel
Andrea B
AB
Hess
Stephen D
SD
Richardson
Stephen K
SK
Lin
Julie H
JH
Benoit
Bernice M
BM
Kasprzycka
Monika
M
Wasik
Mariusz A
MA
Rook
Alain H
AH
D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins / Q000276:immunology* / Q000494:pharmacology; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000378:metabolism / Q000473:pathology; D037181:Lectins, C-Type; D012333:RNA, Messenger / Q000378:metabolism; D053655:Receptors, Interleukin-21 / Q000235:genetics; D012751:Sezary Syndrome / Q000276:immunology* / Q000473:pathology*; D012878:Skin Neoplasms / Q000276:immunology* / Q000473:pathology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000276:immunology; D000098546:Interleukin-21; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018819:Dipeptidyl Peptidase 4; D007371:Interferon-gamma; D007378:Interleukins; D037181:Lectins, C-Type; D012333:RNA, Messenger; D053655:Receptors, Interleukin-21; D000098546:Interleukin-21; D000099192:CD69 Antigens; C042807:DPP4 protein, human