title: Interleukin-21 administration to rhesus macaques chronically infected with simian immunodeficiency virus increases cytotoxic effector molecules in T cells and NK cells and enhances B cell function without increasing immune activation or viral replication.
abstract: We have previously shown that interleukin-21, a pleiotropic C γ-chain signaling cytokine, induces the expression of the cytotoxic molecules granzyme B (GrB) and perforin in vitro in CD8 T cells and NK cells of chronically HIV infected individuals. In this pilot study, four chronically SIV infected rhesus macaques (RM) in late-stage disease were given two doses of recombinant MamuIL-21, 50 μg/kg, intravenously 7 days apart, followed by one subcutaneous dose, 100 μg/kg, 23 days after the second dose. Three animals served as controls. After each dose of IL-21, increases were noted in frequency and mean fluorescence intensity of GrB and perforin expression in memory and effector subsets of CD8 T cells in peripheral blood (PB), in peripheral and mesenteric lymph node (LN) cells, in PB memory and effector CD4 T cells and in NK cells. Frequencies of SIV-gag specific CD107a(+)IFN-γ(+) CD8 T cells increased 3.8-fold in PB and 1.8-fold in LN. In addition, PB CD27(+) memory B cells were 2-fold higher and serum SIV antibodies increased significantly after IL-21 administration. No changes were observed in markers of T cell activation, T cell proliferation or plasma virus load. Thus, administration of IL-21 to chronically SIV infected viremic animals was safe, well tolerated and could augment the cytotoxic potential of T cells and NK cells, promote B cell differentiation with increases in SIV antibody titers without discernable increase in cellular activation. Further studies are warranted to elucidate the effects and potential benefit of IL-21 administration in the context of SIV/HIV infection and in SIV/HIV vaccine design.
authors: Department of Microbiology & Immunology, Developmental centre for AIDS research (D-CFAR), University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors: Suresh
authors: S
authors: Pallikkuth
authors: Kenneth
authors: K
authors: Rogers
authors: Francois
authors: F
authors: Villinger
authors: Melvin
authors: M
authors: Dosterii
authors: Monica
authors: M
authors: Vaccari
authors: Genoveffa
authors: G
authors: Franchini
authors: Rajendra
authors: R
authors: Pahwa
authors: Savita
authors: S
authors: Pahwa
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D053804:Granzymes / Q000276:immunology; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000276:immunology; D007378:Interleukins / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D052118:Lysosomal-Associated Membrane Protein 1 / Q000378:metabolism; D008253:Macaca mulatta / Q000276:immunology* / Q000821:virology; D054353:Perforin / Q000276:immunology; D010865:Pilot Projects; D012367:RNA, Viral / Q000097:blood; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism; D019562:Viral Load; D000098546:Interleukin-21
chemical_list: D000914:Antibodies, Viral; D007378:Interleukins; D052118:Lysosomal-Associated Membrane Protein 1; D012367:RNA, Viral; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D054353:Perforin; D007371:Interferon-gamma; D053804:Granzymes; D000098546:Interleukin-21