tetano
Editor, Senior Moderator
J Virol. 2013 Sep 11. [Epub ahead of print]
Interferon-γ regulates contraction of the influenza-specific CD8 T cell response and limits the size of the memory population.
Prabhu N, Ho AW, Wong KH, Hutchinson PE, Chua YL, Kandasamy M, Lee DC, Sivasankar B, Kemeny DM.
Source
Immunology Programme and Department of Microbiology, National University of Singapore, Singapore.
Abstract
The factors that regulate the contraction of the CD8 T cell response and the magnitude of the memory population against localized mucosal infections like influenza are important for generation of efficient vaccines but are currently undefined. In this study, we use a mouse model of influenza to demonstrate that the absence of IFN-γ or IFN-γR1 leads to aberrant contraction of antigen-specific CD8 T cell responses. The increased accumulation of the effector CD8 T cell population was independent of viral load. Reduced contraction was associated with an increased fraction of CD8 T cells expressing the interleukin-7 receptor at the peak of the response, resulting in enhanced numbers of memory/memory-precursor cells in IFN-γ-/- and IFN-γR-/- compared to WT mice. . Blockade of IL-7 within the lung of IFN-γ-/- mice restored the contraction of flu-specific CD8 T cells, indicating that IL-7R is important for survival and is not simply a consequence of the lack of IFN-γ signaling. Finally, enhanced CD8 T cell recall responses and accelerated viral clearance were observed in the IFN-γ-/- and IFN-γR-/- mice after re-challenge with a heterologous strain of influenza, confirming that higher frequencies of memory precursors are formed in the absence of IFN-γ signaling. In summary, we have identified IFN-γ as an important regulator of localized viral immunity that promotes the contraction of antigen-specific CD8 T cells and inhibits memory precursor formation, thereby limiting the size of the memory cell population after an influenza infection.
PMID:
24027334
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24027334
Interferon-γ regulates contraction of the influenza-specific CD8 T cell response and limits the size of the memory population.
Prabhu N, Ho AW, Wong KH, Hutchinson PE, Chua YL, Kandasamy M, Lee DC, Sivasankar B, Kemeny DM.
Source
Immunology Programme and Department of Microbiology, National University of Singapore, Singapore.
Abstract
The factors that regulate the contraction of the CD8 T cell response and the magnitude of the memory population against localized mucosal infections like influenza are important for generation of efficient vaccines but are currently undefined. In this study, we use a mouse model of influenza to demonstrate that the absence of IFN-γ or IFN-γR1 leads to aberrant contraction of antigen-specific CD8 T cell responses. The increased accumulation of the effector CD8 T cell population was independent of viral load. Reduced contraction was associated with an increased fraction of CD8 T cells expressing the interleukin-7 receptor at the peak of the response, resulting in enhanced numbers of memory/memory-precursor cells in IFN-γ-/- and IFN-γR-/- compared to WT mice. . Blockade of IL-7 within the lung of IFN-γ-/- mice restored the contraction of flu-specific CD8 T cells, indicating that IL-7R is important for survival and is not simply a consequence of the lack of IFN-γ signaling. Finally, enhanced CD8 T cell recall responses and accelerated viral clearance were observed in the IFN-γ-/- and IFN-γR-/- mice after re-challenge with a heterologous strain of influenza, confirming that higher frequencies of memory precursors are formed in the absence of IFN-γ signaling. In summary, we have identified IFN-γ as an important regulator of localized viral immunity that promotes the contraction of antigen-specific CD8 T cells and inhibits memory precursor formation, thereby limiting the size of the memory cell population after an influenza infection.
PMID:
24027334
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24027334