Indoleamine 2,3-Dioxygenase (IDO) Activity during the Primary Immune Response to Influenza Infection Modifies the Memory T Cell Response to Influenza Challenge

Leo K. Sage, Julie M. Fox, Andrew L. Mellor, Stephen M. Tompkins, Ralph A. Tripp

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The generation of a heterosubtypic memory T cell response is important for cross-protective immunity against unrelated strains of influenza virus. One way to facilitate the generation of the memory T cell population is to control the activity of immune modulatory agents. The enzyme, indoleamine 2,3-dioxygenase (IDO), is upregulated during influenza infection by the interferon response where IDO activity depletes tryptophan required in T cell response. In this study, IDO activity was pharmacologically inhibited with 1-methyl-tryptophan (1MT) during the primary response to influenza virus infection and the effect on the memory T cell response was evaluated. 1MT treatment improved the memory T cell response to influenza virus challenge by increasing interferon gamma expression by CD4 and CD8 T cells, and numbers of lung virus-specific CD8+ T cells, and increased the Th1 response as well as modifying the immunodominance hierarchy to increase the number of subdominant epitope specific CD8+ T cells, a feature which may be linked to decreased regulatory T cell function. These changes also accompanied evidence of accelerated lung tissue repair upon virus challenge. These findings suggest that modulation of IDO activity could be exploited in influenza vaccine development to enhance memory T cell responses and reduce disease burden.

Original languageEnglish (US)
Pages (from-to)112-123
Number of pages12
JournalViral Immunology
Volume27
Issue number3
DOIs
StatePublished - Apr 1 2014

Fingerprint

Indoleamine-Pyrrole 2,3,-Dioxygenase
Human Influenza
T-Lymphocytes
Infection
Orthomyxoviridae
Viruses
Lung
Influenza Vaccines
Virus Diseases
Regulatory T-Lymphocytes
Tryptophan
Interferons
Interferon-gamma
Epitopes
Immunity
Cell Count

ASJC Scopus subject areas

  • Immunology
  • Molecular Medicine
  • Virology

Cite this

Indoleamine 2,3-Dioxygenase (IDO) Activity during the Primary Immune Response to Influenza Infection Modifies the Memory T Cell Response to Influenza Challenge. / Sage, Leo K.; Fox, Julie M.; Mellor, Andrew L.; Tompkins, Stephen M.; Tripp, Ralph A.

In: Viral Immunology, Vol. 27, No. 3, 01.04.2014, p. 112-123.

Research output: Contribution to journalArticle

Sage, Leo K. ; Fox, Julie M. ; Mellor, Andrew L. ; Tompkins, Stephen M. ; Tripp, Ralph A. / Indoleamine 2,3-Dioxygenase (IDO) Activity during the Primary Immune Response to Influenza Infection Modifies the Memory T Cell Response to Influenza Challenge. In: Viral Immunology. 2014 ; Vol. 27, No. 3. pp. 112-123.
@article{80b1e25281534ebabcdea7cd98600367,
title = "Indoleamine 2,3-Dioxygenase (IDO) Activity during the Primary Immune Response to Influenza Infection Modifies the Memory T Cell Response to Influenza Challenge",
abstract = "The generation of a heterosubtypic memory T cell response is important for cross-protective immunity against unrelated strains of influenza virus. One way to facilitate the generation of the memory T cell population is to control the activity of immune modulatory agents. The enzyme, indoleamine 2,3-dioxygenase (IDO), is upregulated during influenza infection by the interferon response where IDO activity depletes tryptophan required in T cell response. In this study, IDO activity was pharmacologically inhibited with 1-methyl-tryptophan (1MT) during the primary response to influenza virus infection and the effect on the memory T cell response was evaluated. 1MT treatment improved the memory T cell response to influenza virus challenge by increasing interferon gamma expression by CD4 and CD8 T cells, and numbers of lung virus-specific CD8+ T cells, and increased the Th1 response as well as modifying the immunodominance hierarchy to increase the number of subdominant epitope specific CD8+ T cells, a feature which may be linked to decreased regulatory T cell function. These changes also accompanied evidence of accelerated lung tissue repair upon virus challenge. These findings suggest that modulation of IDO activity could be exploited in influenza vaccine development to enhance memory T cell responses and reduce disease burden.",
author = "Sage, {Leo K.} and Fox, {Julie M.} and Mellor, {Andrew L.} and Tompkins, {Stephen M.} and Tripp, {Ralph A.}",
year = "2014",
month = "4",
day = "1",
doi = "10.1089/vim.2013.0105",
language = "English (US)",
volume = "27",
pages = "112--123",
journal = "Viral Immunology",
issn = "0882-8245",
publisher = "Mary Ann Liebert Inc.",
number = "3",

}

TY - JOUR

T1 - Indoleamine 2,3-Dioxygenase (IDO) Activity during the Primary Immune Response to Influenza Infection Modifies the Memory T Cell Response to Influenza Challenge

AU - Sage, Leo K.

AU - Fox, Julie M.

AU - Mellor, Andrew L.

AU - Tompkins, Stephen M.

AU - Tripp, Ralph A.

PY - 2014/4/1

Y1 - 2014/4/1

N2 - The generation of a heterosubtypic memory T cell response is important for cross-protective immunity against unrelated strains of influenza virus. One way to facilitate the generation of the memory T cell population is to control the activity of immune modulatory agents. The enzyme, indoleamine 2,3-dioxygenase (IDO), is upregulated during influenza infection by the interferon response where IDO activity depletes tryptophan required in T cell response. In this study, IDO activity was pharmacologically inhibited with 1-methyl-tryptophan (1MT) during the primary response to influenza virus infection and the effect on the memory T cell response was evaluated. 1MT treatment improved the memory T cell response to influenza virus challenge by increasing interferon gamma expression by CD4 and CD8 T cells, and numbers of lung virus-specific CD8+ T cells, and increased the Th1 response as well as modifying the immunodominance hierarchy to increase the number of subdominant epitope specific CD8+ T cells, a feature which may be linked to decreased regulatory T cell function. These changes also accompanied evidence of accelerated lung tissue repair upon virus challenge. These findings suggest that modulation of IDO activity could be exploited in influenza vaccine development to enhance memory T cell responses and reduce disease burden.

AB - The generation of a heterosubtypic memory T cell response is important for cross-protective immunity against unrelated strains of influenza virus. One way to facilitate the generation of the memory T cell population is to control the activity of immune modulatory agents. The enzyme, indoleamine 2,3-dioxygenase (IDO), is upregulated during influenza infection by the interferon response where IDO activity depletes tryptophan required in T cell response. In this study, IDO activity was pharmacologically inhibited with 1-methyl-tryptophan (1MT) during the primary response to influenza virus infection and the effect on the memory T cell response was evaluated. 1MT treatment improved the memory T cell response to influenza virus challenge by increasing interferon gamma expression by CD4 and CD8 T cells, and numbers of lung virus-specific CD8+ T cells, and increased the Th1 response as well as modifying the immunodominance hierarchy to increase the number of subdominant epitope specific CD8+ T cells, a feature which may be linked to decreased regulatory T cell function. These changes also accompanied evidence of accelerated lung tissue repair upon virus challenge. These findings suggest that modulation of IDO activity could be exploited in influenza vaccine development to enhance memory T cell responses and reduce disease burden.

UR - http://www.scopus.com/inward/record.url?scp=84919415464&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84919415464&partnerID=8YFLogxK

U2 - 10.1089/vim.2013.0105

DO - 10.1089/vim.2013.0105

M3 - Article

C2 - 24702331

AN - SCOPUS:84919415464

VL - 27

SP - 112

EP - 123

JO - Viral Immunology

JF - Viral Immunology

SN - 0882-8245

IS - 3

ER -