Katherine M Eichinger1,2, Jessica L Kosanovich1, Kerry M Empey1,2,3,4. 1. Department of Pharmacy and Therapeutics, University of Pittsburgh School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania. 2. Center for Clinical Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania. 3. Department of Immunology, University of Pittsburgh School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania. 4. Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, Pennsylvania.
Abstract
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.
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 infectedinfantmice 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.
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