Protective influenza-specific CD8 T cell responses require interactions with dendritic cells in the lungs.
Influenza infections induce a rapid, but transient, dendritic cell (DC) migration from the lungs to the lymph nodes (LNs) that is followed by substantial recruitment of DCs into the lungs without subsequent migration to the LNs. Given that peripheral DCs are primarily thought to be involved in the initiation of adaptive immunity after migration into lymphoid tissues, what role these newly lung-recruited DCs play in influenza virus immunity is unclear. In this study, we demonstrate that loss of non-LN migratory pulmonary DC subsets increases mortality, sustains higher viral titers, and impairs pulmonary CD8 T cell responses. Reconstitution of the lungs with pulmonary plasmacytoid DCs, CD8+ DCs, or interstitial DCs restores CD8 T cell responses in a cell contact-, major histocompatability complex I-, and influenza peptide-dependent manner. Thus, after their initial activation in the LN, protective influenza-specific CD8 T cell responses require additional antigen-dependent interactions, specifically with DCs in the lungs.
McGill
Jodi
J
Department of Pathology, Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52241, USA.
Van Rooijen
Nico
N
Legge
Kevin L
KL
D000818:Animals; D016827:CD8 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002450:Cell Communication / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology*; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D053121:Influenza A Virus, H2N2 Subtype / Q000276:immunology*; D008168:Lung / Q000276:immunology* / Q000821:virology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D010455:Peptides / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology
D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; D015395:Histocompatibility Antigens Class I; D010455:Peptides; D014764:Viral Proteins