Abstract
Infection with human immunodeficiency virus (HIV)-1 induces a progressive deterioration of the immune system that ultimately leads to acquired immune deficiency syndrome (AIDS). Murine models indicate that the common γ-chain (γ(c))-sharing cytokine interleukin (IL)-21 and its receptor (IL-21R) play a crucial role in maintaining polyfunctional T cell responses during chronic viral infections. Therefore, we analyzed the ability of this cytokine to modulate the properties of human CD8 T cells in comparison with other γ(c)-sharing cytokines (IL-2, IL-7, and IL-15). CD8 T cells from healthy volunteers were stimulated in vitro via T cell receptor signals to mimic the heightened status of immune activation of HIV-infected patients. The administration of IL-21 upregulated cytotoxic effector function and the expression of the costimulatory molecule CD28. Notably, this outcome was not accompanied by increased cellular proliferation or activation. Moreover, IL-21 promoted antiviral activity while not inducing HIV-1 replication in vitro. Thus, IL-21 may be a favorable molecule for immunotherapy and a suitable vaccine adjuvant in HIV-infected individuals.
Copyright © 2011 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.
Publication types
-
Research Support, N.I.H., Extramural
MeSH terms
-
Adjuvants, Immunologic / metabolism
-
Adjuvants, Immunologic / pharmacology*
-
Adjuvants, Immunologic / therapeutic use
-
Animals
-
CD28 Antigens / immunology
-
CD28 Antigens / metabolism
-
CD8-Positive T-Lymphocytes / immunology*
-
CD8-Positive T-Lymphocytes / metabolism
-
Cells, Cultured
-
Granzymes / analysis
-
HIV Infections / drug therapy
-
HIV Infections / immunology
-
HIV Infections / metabolism
-
HIV-1 / drug effects*
-
HIV-1 / immunology
-
HIV-1 / metabolism
-
Humans
-
Immunity, Cellular / drug effects
-
Interleukin-15 / immunology
-
Interleukin-15 / pharmacology
-
Interleukin-2 / immunology
-
Interleukin-2 / metabolism
-
Interleukin-7 / immunology
-
Interleukin-7 / metabolism
-
Interleukins / immunology*
-
Interleukins / metabolism
-
Interleukins / pharmacology*
-
Lymphocyte Activation / drug effects
-
Lymphocyte Activation / immunology
-
Mice
-
Perforin / analysis
-
Receptors, Antigen, T-Cell / immunology
-
Receptors, Antigen, T-Cell / metabolism
-
Signal Transduction / drug effects
-
Signal Transduction / immunology
-
Viral Load
-
Virus Replication / drug effects
-
Virus Replication / immunology
Substances
-
Adjuvants, Immunologic
-
CD28 Antigens
-
Interleukin-15
-
Interleukin-2
-
Interleukin-7
-
Interleukins
-
Receptors, Antigen, T-Cell
-
Perforin
-
Granzymes
-
interleukin-21