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 language | English (US) |
|---|---|
| Pages (from-to) | 112-123 |
| Number of pages | 12 |
| Journal | Viral Immunology |
| Volume | 27 |
| Issue number | 3 |
| DOIs | |
| State | Published - Apr 1 2014 |
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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 journal › Article
}
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.
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U2 - 10.1089/vim.2013.0105
DO - 10.1089/vim.2013.0105
M3 - Article
VL - 27
SP - 112
EP - 123
JO - Viral Immunology
JF - Viral Immunology
SN - 0882-8245
IS - 3
ER -