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An In vitro Model to Study Immune Responses of Human Peripheral Blood Mononuclear Cells to Human Respiratory Syncytial Virus Infection
Published on: December 10, 2013
Localization of the T-cell response to RSV infection is altered in infant mice
Katherine M Eichinger1,2, Jessica L Kosanovich1, Kerry M Empey1,2,3,4
1Department of Pharmacy and Therapeutics, University of Pittsburgh School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania.
Insights
Infant mice infected with respiratory syncytial virus (RSV) show T-cell deficiencies in the airways. Early intranasal interferon-gamma (IFN-γ) boosts RSV-specific CD8+ T-cells in infant lungs, suggesting a potential therapeutic avenue.
Area of Science:
- Immunology
- Virology
- Pediatrics
Background:
- Respiratory syncytial virus (RSV) is a major cause of severe respiratory illness in infants.
- Infant T-cell responses in the airways during RSV infection are not well understood.
- Stronger Th1 responses correlate with less severe RSV disease in infants.
Purpose of the Study:
- To compare T-cell localization in the airways of infant and adult mice infected with RSV.
- To investigate the impact of local interferon-gamma (IFN-γ) administration on infant T-cell immunity during RSV infection.
- To test the hypothesis of quantitative and qualitative T-cell deficiencies in RSV-infected infant airways.
Main Methods:
- Comparison of T-cell populations (CD4+, CD8+) in bronchoalveolar lavage fluid of infant and adult RSV-infected mice.
- Assessment of T-cell localization (lung tissue vs. airway) and T-bet expression.
- Administration of local IFN-γ to infant airways and intranasal IFN-γ to assess effects on T-cell responses.
Main Results:
- Adult mice showed accumulation of CD8+ and CD4+ Tbet+ T-cells in alveolar spaces; infants had even distribution of CD4+ Tbet+ T-cells.
- Infant lungs had higher frequencies of CD8+ T-cells compared to adults.
- Local IFN-γ administration did not increase airspace T-cells and reduced CD4+ Tbet+ T-cells, but intranasal IFN-γ increased RSV F protein-specific CD8+ T-cells in the alveolar space.
Conclusions:
- Infant T-cell responses to RSV exhibit quantitative and qualitative defects.
- Early, local administration of IFN-γ can enhance the RSV-specific CD8+ T-cell response in the infant airway.
- These findings highlight potential therapeutic strategies targeting infant T-cell immunity against RSV.
Objectives:
Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections worldwide, causing disproportionate morbidity and mortality in infants and children. Infants with stronger Th1 responses have less severe disease, yet little is known about the infant T-cell response within the air space. Thus, we tested the hypothesis that RSV infected infant mice would have quantitative and qualitative deficiencies in CD4+ and CD8+ T-cell populations isolated from the bronchoalveolar lavage when compared to adults and that local delivery of IFN-γ would increase airway CD4+ Tbet+ and CD8+ Tbet+ T-cell responses.
Methods:
We compared the localization of T-cell responses in RSV-infected infant and adult mice and investigated the effects of local IFN-γ administration on infant cellular immunity.
Results:
Adult CD8+ CD44HI and CD4+ CD44HI Tbet+ T-cells accumulated in the alveolar space whereas CD4+ CD44HI Tbet+ T-cells were evenly distributed between the infant lung tissue and airway and infant lungs contained higher frequencies of CD8+ T-cells. Delivery of IFN-γ to the infant airway failed to increase the accumulation of T-cells in the airspace and unexpectedly reduced CD4+ CD44HI Tbet+ T-cells. However, intranasal IFN-γ increased RSV F protein-specific CD8+ T-cells in the alveolar space.
Conclusion:
Together, these data suggest that quantitative and qualitative defects exist in the infant T-cell response to RSV but early, local IFN-γ exposure can increase the CD8+ RSV-specific T-cell response.
