Document Detail


Interleukin-21 and cellular activation concurrently induce potent cytotoxic function and promote antiviral activity in human CD8 T cells.
MedLine Citation:
PMID:  20977918     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Anita Parmigiani; Maria F Pallin; Helena Schmidtmayerova; Mathias G Lichtenheld; Savita Pahwa
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-10-25
Journal Detail:
Title:  Human immunology     Volume:  72     ISSN:  1879-1166     ISO Abbreviation:  Hum. Immunol.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-17     Completed Date:  2011-06-29     Revised Date:  2012-02-02    
Medline Journal Info:
Nlm Unique ID:  8010936     Medline TA:  Hum Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  115-23     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.
Affiliation:
Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, Florida, USA.
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MeSH Terms
Descriptor/Qualifier:
Adjuvants, Immunologic / metabolism,  pharmacology*,  therapeutic use
Animals
Antigens, CD28 / immunology,  metabolism
CD8-Positive T-Lymphocytes / immunology*,  metabolism
Cells, Cultured
Granzymes / analysis
HIV Infections / drug therapy,  immunology,  metabolism
HIV-1 / drug effects*,  immunology,  metabolism
Humans
Immunity, Cellular / drug effects
Interleukin-15 / immunology,  pharmacology
Interleukin-2 / immunology,  metabolism
Interleukin-7 / immunology,  metabolism
Interleukins / immunology*,  metabolism,  pharmacology*
Lymphocyte Activation / drug effects,  immunology
Mice
Perforin / analysis
Receptors, Antigen, T-Cell / immunology,  metabolism
Signal Transduction / drug effects,  immunology
Viral Load
Virus Replication / drug effects,  immunology
Grant Support
ID/Acronym/Agency:
5P30AI073961/AI/NIAID NIH HHS; AI077501/AI/NIAID NIH HHS; R01 AI077501-01/AI/NIAID NIH HHS; R01 AI077501-02/AI/NIAID NIH HHS; R01 AI077501-03/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Adjuvants, Immunologic; 0/Antigens, CD28; 0/Interleukin-15; 0/Interleukin-2; 0/Interleukin-7; 0/Interleukins; 0/Receptors, Antigen, T-Cell; 0/interleukin-21; 126465-35-8/Perforin; EC 3.4.21.-/Granzymes

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