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

Suresh Pallikkuth, Kenneth Rogers, Francois Villinger, Melvin Dosterii, Monica Vaccari, Genoveffa Franchini, Rajendra Pahwa, Savita Pahwa

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41 Scopus citations

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, 50μg/kg, intravenously 7 days apart, followed by one subcutaneous dose, 100μg/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.

Original languageEnglish (US)
Pages (from-to)9229-9238
Number of pages10
JournalVaccine
Volume29
Issue number49
DOIs
StatePublished - Nov 15 2011

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Keywords

  • B cells
  • Interleukin-21
  • Natural killer cells
  • Rhesus macaques
  • SIV
  • T cells

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)
  • Molecular Medicine

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