title: Interleukin-21 up-regulates interleukin-21R expression and interferon gamma production by CD8+ cells in SHIV-infected macaques.
abstract: Interleukin-21 (IL-21) is produced primarily by CD4+ T cells and regulates immunity against human/simian immunodeficiency virus (HIV/SIV) infection. Activated CD8+ cells and their secreted interferon-gamma (IFN-γ) are crucial for the control of acute HIV/SIV infection. However, whether IL-21 can regulate IFN-γ production by CD8+ cells remains controversial. Rhesus macaques (RMs, n = 8) were infected with SHIV and the levels of plasma IL-21, IFN-γ and the frequency of peripheral blood activated T cells were measured longitudinally. Following infection with SHIV, the levels of plasma IL-21 and IFN-γ increased, peaked at 17 days postinfection and declined later. Furthermore, IL-21 induced IL-21 receptor (IL-21R) and IFN-γ, perforin, but not granmyze B, expression in CD8+ cells from four selected SHIV-infected RMs. The regulatory effect of IL-21 on CD8+ cell function appeared to be associated with increased levels of STAT3, but not STAT5, phosphorylation in CD8+ cells from SHIV-infected RMs. In parallel, treatment with soluble IL-21R/Fc, an inhibitor of IL-21-induced activation of JAK1/3 and STAT3, abrogated IL-21-induced STAT3 activation and IFN-γ production in CD8+ cells from SHIV-infected RMs in vitro. Our data indicated that IL-21 was a positive regulator of IFN-γ-secreting CD8+ cells and increased the STAT3 phosphorylation, regulating T-cell immunity against acute SHIV infection in RMs. Our findings may provide a new basis for the development of immunotherapies for the control of SHIV/HIV infection.
authors.affiliation: Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medical Center, Peking Union Medical College, No. 5 Panjiayuan Nanli, Chaoyang Dist, Beijing 100021.
authors.forename: Chang-cheng
authors.initials: CC
authors.lastname: Zhao
authors.forename: Xi-qiang
authors.initials: XQ
authors.lastname: Gao
authors.forename: Jing
authors.initials: J
authors.lastname: Xue
authors.forename: Zhe
authors.initials: Z
authors.lastname: Cong
authors.forename: Wei-lun
authors.initials: WL
authors.lastname: Zhang
authors.forename: Ting
authors.initials: T
authors.lastname: Chen
authors.forename: Fang-xin
authors.initials: FX
authors.lastname: Wu
authors.forename: Jing
authors.initials: J
authors.lastname: Xiong
authors.forename: Bin
authors.initials: B
authors.lastname: Ju
authors.forename: Aihua
authors.initials: A
authors.lastname: Su
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wei
authors.forename: Chuan
authors.initials: C
authors.lastname: Qin
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D006678:HIV; D015658:HIV Infections / Q000378:metabolism / Q000473:pathology / Q000662:veterinary; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000378:metabolism*; D007378:Interleukins / Q000494:pharmacology*; D008253:Macaca mulatta; D008297:Male; D008992:Monkey Diseases / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D054353:Perforin / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D053655:Receptors, Interleukin-21 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016097:Simian Acquired Immunodeficiency Syndrome / Q000378:metabolism / Q000473:pathology; D015302:Simian Immunodeficiency Virus; D015854:Up-Regulation / Q000187:drug effects*; D000098546:Interleukin-21
chemical_list: D007378:Interleukins; D053655:Receptors, Interleukin-21; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; D054353:Perforin; D007371:Interferon-gamma; D000098546:Interleukin-21
keywords: IL-21 receptor; STAT3; Simian/human immunodeficiency virus; T-cell; interferon-gamma; interleukin-21