tetano
Editor, Senior Moderator
Viral Immunol. 2014 Apr 4. [Epub ahead of print]
Indoleamine 2,3-Dioxygenase (IDO) Activity During the Primary Immune Response to Influenza Infection Modifies the Memory T Cell Response to Influenza Challenge.
Sage LK1, Fox JM, Mellor AL, Tompkins SM, Tripp RA.
Author information
11 University of Georgia , College of Veterinary Medicine, Department of Infectious Diseases, Athens, Georgia .
Abstract
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.
PMID:
24702331
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24702331
Indoleamine 2,3-Dioxygenase (IDO) Activity During the Primary Immune Response to Influenza Infection Modifies the Memory T Cell Response to Influenza Challenge.
Sage LK1, Fox JM, Mellor AL, Tompkins SM, Tripp RA.
Author information
11 University of Georgia , College of Veterinary Medicine, Department of Infectious Diseases, Athens, Georgia .
Abstract
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.
PMID:
24702331
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24702331