Localization of the T-cell response to RSV infection is altered in infant mice

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⁺ CD44^HI and CD4⁺ CD44^HI Tbet⁺ T-cells accumulated in the alveolar space whereas CD4⁺ CD44^HI 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⁺ CD44^HI 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.

Keywords: IFN-γ; RSV; T-cell response; airway; infant mice.