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 G Pahwa

Research output: Contribution to journalArticle

40 Citations (Scopus)

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

Fingerprint

Simian immunodeficiency virus
Virus Activation
Simian Immunodeficiency Virus
natural killer cells
virus replication
Macaca mulatta
Natural Killer Cells
B-lymphocytes
B-Lymphocytes
T-lymphocytes
T-Lymphocytes
blood
SAIDS Vaccines
dosage
lymph nodes
Lymph Nodes
AIDS Vaccines
Antibodies
T-Lymphocyte Subsets
antibodies

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

Cite this

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

In: Vaccine, Vol. 29, No. 49, 15.11.2011, p. 9229-9238.

Research output: Contribution to journalArticle

@article{cb94ca98cb7e44208c71b7aad6ed83c3,
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, 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.",
keywords = "B cells, Interleukin-21, Natural killer cells, Rhesus macaques, SIV, T cells",
author = "Suresh Pallikkuth and Kenneth Rogers and Francois Villinger and Melvin Dosterii and Monica Vaccari and Genoveffa Franchini and Rajendra Pahwa and Pahwa, {Savita G}",
year = "2011",
month = "11",
day = "15",
doi = "10.1016/j.vaccine.2011.09.118",
language = "English",
volume = "29",
pages = "9229--9238",
journal = "Vaccine",
issn = "0264-410X",
publisher = "Elsevier BV",
number = "49",

}

TY - JOUR

T1 - 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

AU - Pallikkuth, Suresh

AU - Rogers, Kenneth

AU - Villinger, Francois

AU - Dosterii, Melvin

AU - Vaccari, Monica

AU - Franchini, Genoveffa

AU - Pahwa, Rajendra

AU - Pahwa, Savita G

PY - 2011/11/15

Y1 - 2011/11/15

N2 - 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.

AB - 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.

KW - B cells

KW - Interleukin-21

KW - Natural killer cells

KW - Rhesus macaques

KW - SIV

KW - T cells

UR - http://www.scopus.com/inward/record.url?scp=82555187124&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=82555187124&partnerID=8YFLogxK

U2 - 10.1016/j.vaccine.2011.09.118

DO - 10.1016/j.vaccine.2011.09.118

M3 - Article

VL - 29

SP - 9229

EP - 9238

JO - Vaccine

JF - Vaccine

SN - 0264-410X

IS - 49

ER -