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Am J Respir Crit Care Med. 2012 Oct 18. [Epub ahead of print]
High Levels of Virus-specific CD4+ T Cells Predict Severe Pandemic Influenza A Virus Infection.
Zhao Y, Zhang YH, Denney L, Young D, Powell TJ, Peng YC, Li N, Yan HP, Wang DY, Shu YL, Kendrick Y, McMichael AJ, Ho LP, Dong T.
Source
Capital Medical University, BeJing You'an Hospital, Beijing, China.
Abstract
RATIONALE:
T cell responses have been implicated in both control and exacerbation of lung injury during influenza A virus (IAV) infection.
OBJECTIVES:
To examine the breadth and magnitude of influenza-specific CD4+ and CD8+ T cell responses during acute phase of infection.
METHODS:
Influenza-specific T cell response to the entire pandemic H1N1/09 influenza A virus proteome and T cell-related cytokine levels were measured in blood from previously healthy individuals with mild (n=32) and severe (n=16) IAV infection during the 2009 influenza pandemic. Virus-specific T cell response in lung and blood was also performed in two acutely infected, severely ill patients using fluorescent-conjugated pdmH1N1/09 Matrix-MHC-I tetrameric complexes.
MAIN RESULTS:
Strong and broad CD4+ but not CD8+ T cell responses were observed in the blood, and were higher in those with severe disease. Antigen-specific CD8+ T cells in the lungs were on average, 45-fold higher compared to blood in both severely ill patients. Paradoxically, in patients with severe disease, IL-17, IL-2, IL-4 and IFN-γ levels were significantly decreased.
CONCLUSION:
High levels of circulating virus-specific CD4+ T cells to two viral internal proteins (nucleoprotein and matrix) in the first phase of infection is associated with subsequent development of severe IAV infection. This finding could be an early and specific marker for ensuing clinical deterioration. Differential levels of antigen-specific CD8+ T cells in lungs and blood have implications on design and analysis of clinical of trials for T cell vaccines since measurements of T cells in the periphery may not reflect events in the lungs.
PMID:
23087026
[PubMed - as supplied by publisher]
High Levels of Virus-specific CD4+ T Cells Predict Severe Pandemic Influenza A Virus Infection.
Zhao Y, Zhang YH, Denney L, Young D, Powell TJ, Peng YC, Li N, Yan HP, Wang DY, Shu YL, Kendrick Y, McMichael AJ, Ho LP, Dong T.
Source
Capital Medical University, BeJing You'an Hospital, Beijing, China.
Abstract
RATIONALE:
T cell responses have been implicated in both control and exacerbation of lung injury during influenza A virus (IAV) infection.
OBJECTIVES:
To examine the breadth and magnitude of influenza-specific CD4+ and CD8+ T cell responses during acute phase of infection.
METHODS:
Influenza-specific T cell response to the entire pandemic H1N1/09 influenza A virus proteome and T cell-related cytokine levels were measured in blood from previously healthy individuals with mild (n=32) and severe (n=16) IAV infection during the 2009 influenza pandemic. Virus-specific T cell response in lung and blood was also performed in two acutely infected, severely ill patients using fluorescent-conjugated pdmH1N1/09 Matrix-MHC-I tetrameric complexes.
MAIN RESULTS:
Strong and broad CD4+ but not CD8+ T cell responses were observed in the blood, and were higher in those with severe disease. Antigen-specific CD8+ T cells in the lungs were on average, 45-fold higher compared to blood in both severely ill patients. Paradoxically, in patients with severe disease, IL-17, IL-2, IL-4 and IFN-γ levels were significantly decreased.
CONCLUSION:
High levels of circulating virus-specific CD4+ T cells to two viral internal proteins (nucleoprotein and matrix) in the first phase of infection is associated with subsequent development of severe IAV infection. This finding could be an early and specific marker for ensuing clinical deterioration. Differential levels of antigen-specific CD8+ T cells in lungs and blood have implications on design and analysis of clinical of trials for T cell vaccines since measurements of T cells in the periphery may not reflect events in the lungs.
PMID:
23087026
[PubMed - as supplied by publisher]
