tetano
Editor, Senior Moderator
Clin Exp Immunol. 2013 Aug 13. doi: 10.1111/cei.12186. [Epub ahead of print]
Influenza infection results in local expansion of memory CD8+ T cells with antigen-nonspecific phenotype and function.
Tietze JK, Sckisel GD, Zamora AE, Hsiao HH, Priest SO, Wilkins DE, Lanier LL, Blazar BR, Baumgarth N, Murphy WJ.
Source
Department of Dermatology, School of Medicine, University of California, Davis, Sacramento, CA.
Abstract
Primary viral infections induce activation of CD8+ T cells responsible for effective resistance. We sought to characterize the nature of the CD8+ T cell expansion observed after primary viral infection with influenza. Infection of na?ve mice with different strains of influenza resulted in rapid expansion of memory CD8+ T cells exhibiting a unique bystander phenotype with significant up-regulation of NKG2D, but not CD25, on the CD44high CD8+ T cells, suggesting an antigen-nonspecific phenotype. We further confirmed the non-specificity of this phenotype on Ovalbumin-specific (OT-I) CD8+ T cells, which are not specific to influenza. These nonspecific CD8+ T cells also displayed increased lytic capabilities and were primarily observed in the lung. Thus, influenza infection was shown to induce a rapid, antigen-nonspecific memory T cell expansion which is restricted to the specific site of inflammation. In contrast, CD8+ T cells of a similar phenotype could be observed in other organs following administration of systemic agonistic anti-CD40 and interleukin-2 immunotherapy demonstrating that bystander expansion in multiple sites is possible depending on whether the nature of activation is either acute or systemic. Finally, intranasal blockade of NKG2D resulted in a significant increase in viral replication early during the course of infection suggesting that NKG2D is a critical mediator of anti-influenza responses prior to the initiation of adaptive immunity. These results further characterize the local bystander expansion of tissue-resident, memory CD8+ T cells, which, due to their early induction, may play an important NKG2D-mediated, antigen-nonspecific role during the early stages of viral infection.
This article is protected by copyright. All rights reserved.
KEYWORDS:
Bystander activation, NKG2D, antigen non-specific, memory CD8, tissue resident
PMID:
23937663
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23937663
Influenza infection results in local expansion of memory CD8+ T cells with antigen-nonspecific phenotype and function.
Tietze JK, Sckisel GD, Zamora AE, Hsiao HH, Priest SO, Wilkins DE, Lanier LL, Blazar BR, Baumgarth N, Murphy WJ.
Source
Department of Dermatology, School of Medicine, University of California, Davis, Sacramento, CA.
Abstract
Primary viral infections induce activation of CD8+ T cells responsible for effective resistance. We sought to characterize the nature of the CD8+ T cell expansion observed after primary viral infection with influenza. Infection of na?ve mice with different strains of influenza resulted in rapid expansion of memory CD8+ T cells exhibiting a unique bystander phenotype with significant up-regulation of NKG2D, but not CD25, on the CD44high CD8+ T cells, suggesting an antigen-nonspecific phenotype. We further confirmed the non-specificity of this phenotype on Ovalbumin-specific (OT-I) CD8+ T cells, which are not specific to influenza. These nonspecific CD8+ T cells also displayed increased lytic capabilities and were primarily observed in the lung. Thus, influenza infection was shown to induce a rapid, antigen-nonspecific memory T cell expansion which is restricted to the specific site of inflammation. In contrast, CD8+ T cells of a similar phenotype could be observed in other organs following administration of systemic agonistic anti-CD40 and interleukin-2 immunotherapy demonstrating that bystander expansion in multiple sites is possible depending on whether the nature of activation is either acute or systemic. Finally, intranasal blockade of NKG2D resulted in a significant increase in viral replication early during the course of infection suggesting that NKG2D is a critical mediator of anti-influenza responses prior to the initiation of adaptive immunity. These results further characterize the local bystander expansion of tissue-resident, memory CD8+ T cells, which, due to their early induction, may play an important NKG2D-mediated, antigen-nonspecific role during the early stages of viral infection.
This article is protected by copyright. All rights reserved.
KEYWORDS:
Bystander activation, NKG2D, antigen non-specific, memory CD8, tissue resident
PMID:
23937663
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23937663