1314. Cytotoxic CD8 T cells and Th1 Cytokines Mediate Mucosal Immunity to Respiratory Viral Infection in Neonates and Infants
Session: Poster Abstract Session: Biomarkers and Correlates of Protection
Saturday, October 5, 2013
Room: The Moscone Center: Poster Hall C
Posters
  • 42147_IDWposter.pdf (1.8 MB)
  • Background:

    Respiratory viral infection (RVI) is a major cause of illness and mortality in infants worldwide; however the reason for this increased susceptibility is unknown.  Our studies in mice have shown the importance of lung versus peripheral blood (PB) effector-memory T cells in protection from respiratory viruses.  To assess whether effector memory T cells (TEM) are recruited to the lungs of infants during RVI, we used a novel analysis of immune cells and cytokines from endotracheal tube (ETT) fluid obtained daily from 19 infants (aged 0.5-24 months) with RVI requiring mechanical ventilation and 10 control infants (2-21 months) intubated for non-pulmonary reasons. 

    Methods:

    RVI was diagnosed by PCR.  Flow cytometry was used to assess ETT cellular content and phenotype.  Luminex was used to measure 25 chemokines and cytokines from ETT supernatant.

    Results:

    Viral pathogens were rhinovirus (5), respiratory syncytial virus (8), human metapneumovirus (4) and coronavirus (2).  Most cells in ETT fluid from infected infants and controls were innate immune cells, such as neutrophils, macrophages and monocytes.  CD3+ T cells were found in all infected infants, but were rare in controls (p=0.06).  T cells in ETT fluid were distinct from those in PB, being mainly CD8+(CD4:CD8 ratio ETT 0.79±0.2 versus PB 3.1 ±1.7, p=0.006) with an effector memory phenotype compared to the naïve phenotype of PB T cells (memory:naïve ratio ETT 7.05±3 versus PB 0.11±0.04, p<0.0001).  In infected infants, the percentage of CD8 T cells peaked at day 5 (CD4:CD8 infected 0.067±0.07 versus control 1.41±0.167) and expressed CD107, a marker of cytotoxic degranulation (17.59 percent of CD8 T cells ± 2.55).  IL-15, a cytokine important for long-term survival and proliferation of CD8 T cells, was elevated in the ETT fluid of infected infants (infected 408.8 ± 82.5 versus controls 54.84 ± 1.4, p= 0.019) as was the Th1 promoting cytokine IFN-γ (16.9± 4.4 versus controls 0.63 ± 0.54, p=0.04), but not Th2 cytokines IL-4, IL-5 or IL-13. 

    Conclusion:

    Our results show airway migration of cytotoxic CD8 effector memory T cells and a polarized Th1 immune response to RVI occurs in infants.  These findings offer new insight into how infant mucosal immunity is established and may contribute to the development of future diagnostics, immunotherapies and vaccines to accelerate this process and improve outcomes.

    Kara Bickham, MD1, Claire Gordon2, John Scott Baird, MD3, Thyyar Ravindranath, MD3, Thomas Connors, MD3 and Donna Farber, PhD4, (1)Medicine, Columbia University, New York, NY, (2)Division of Infectious Diseases, Department of Medicine, Columbia University Medical Center, New York, NY, (3)Pediatric Critical Care, Columbia University, New York, NY, (4)Surgery, Columbia University, New York, NY

    Disclosures:

    K. Bickham, None

    C. Gordon, None

    J. S. Baird, None

    T. Ravindranath, None

    T. Connors, None

    D. Farber, None

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