IL-15 trans-presentation by pulmonary dendritic cells promotes effector CD8 T cell survival during influenza virus infection.
We have recently demonstrated that peripheral CD8 T cells require two separate activation hits to accumulate to high numbers in the lungs after influenza virus infection: a primary interaction with mature, antigen-bearing dendritic cells (DCs) in the lymph node, and a second, previously unrecognized interaction with MHC I-viral antigen-bearing pulmonary DCs in the lungs. We demonstrate that in the absence of lung-resident DC subsets, virus-specific CD8 T cells undergo significantly increased levels of apoptosis in the lungs; however, reconstitution with pulmonary plasmacytoid DCs and CD8alpha(+) DCs promotes increased T cell survival and accumulation in the lungs. Further, our results show that the absence of DCs after influenza virus infection results in significantly reduced levels of IL-15 in the lungs and that pulmonary DC-mediated rescue of virus-specific CD8 T cell responses in the lungs requires trans-presentation of IL-15 via DC-expressed IL-15Ralpha. This study demonstrates a key, novel requirement for DC trans-presented IL-15 in promoting effector CD8 T cell survival in the respiratory tract after virus infection, and suggests that this trans-presentation could be an important target for the development of unique antiviral therapies and more effective vaccine strategies.
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; D000998:Antiviral Agents / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D002455:Cell Division; D002470:Cell Survival; D003713:Dendritic Cells / Q000276:immunology*; D015195:Drug Design; D006801:Humans; D007251:Influenza, Human / Q000276:immunology*; D019409:Interleukin-15 / Q000378:metabolism*; D008168:Lung / Q000276:immunology* / Q000821:virology; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal
D000998:Antiviral Agents; D019409:Interleukin-15