Pulmonary DC:T cell interactions following influenza A virus challenge and vaccination

After influenza A virus (IAV) infection dendritic cells (DC) in the lungs migrate to the lung-draining lymph node where they interact with and activate naïve IAV-specific CD8 T cells. These primed CD8 T cells then undergo expansion and migrate back to the lungs where they target and kill IAV infected cells. Previous work in the Legge laboratory has demonstrated that in addition to the interaction in the lymph nodes, IAV-specific CD8 T cells require a second engagement with pDC and CD8α+ DC in the lungs. This second interaction is necessary to allow IAV-specific CD8 T cells to expand to the numbers needed to clear infection. My studies are aimed at determining the pulmonary localization and kinetics of this DC:T cell interaction in the lungs after IAV infection. I am also interested in elucidating the role of these interactions during intranasal IAV vaccinations. These studies will provide insight towards defining the factors needed to mediate proper immunity to IAV, and potentially other respiratory virus infections. Further, these studies may also suggest targets whose expression could be altered to allow boosting or dampening of pulmonary immunity when inappropriate or insufficient pulmonary immune responses are generated.

Carlin LE, Hemann EA, Zacharias ZR, Heusel JW, Legge KL. Natural Killer Cell Recruitment to the Lung During Influenza A Virus Infection Is Dependent on CXCR3, CCR5, and Virus Exposure Dose. Front Immunol. 2018 Apr 17;9:781. doi:10.3389/fimmu.2018.00781. eCollection 2018. PubMed PMID: 29719539; PubMed Central PMCID: PMC5913326.

Hemann EA, Sjaastad LE, Langlois RA, Legge KL. Plasmacytoid Dendritic Cells Require Direct Infection To Sustain the Pulmonary Influenza A Virus-Specific CD8 T Cell Response. J Virol. 2015 Dec 30;90(6):2830-7. doi: 10.1128/JVI.02546-15. PubMed PMID: 26719269; PubMed Central PMCID: PMC4810669.

Hemann EA, McGill JL, Legge KL. Chronic ethanol exposure selectively inhibits the influenza-specific CD8 T cell response during influenza a virus infection. Alcohol Clin Exp Res. 2014 Sep;38(9):2403-13. doi: 10.1111/acer.12522. Epub 2014 Aug 26. PubMed PMID: 25160044; PubMed Central PMCID: PMC4461571.

Khan SH, Hemann EA, Legge KL, Norian LA, Badovinac VP. Diet-induced obesity does not impact the generation and maintenance of primary memory CD8 T cells. J Immunol. 2014 Dec 15;193(12):5873-82. doi: 10.4049/jimmunol.1401685. Epub 2014 Nov 5. PubMed PMID: 25378592; PubMed Central PMCID: PMC4372810.

Hemann EA, Legge KL. Peripheral regulation of T cells by dendritic cells during infection. Immunol Res. 2014 Aug;59(1-3):66-72. doi:10.1007/s12026-014-8530-3. Review. PubMed PMID: 24838143.

Hemann EA, Kang SM, Legge KL. Protective CD8 T cell-mediated immunity against influenza A virus infection following influenza virus-like particle vaccination. J Immunol. 2013 Sep 1;191(5):2486-94. doi: 10.4049/jimmunol.1300954. Epub 2013 Jul 24. PubMed PMID: 23885108; PubMed Central PMCID: PMC3777857.

Brincks EL, Gurung P, Langlois RA, Hemann EA, Legge KL, Griffith TS. The magnitude of the T cell response to a clinically significant dose of influenza virus is regulated by TRAIL. J Immunol. 2011 Nov 1;187(9):4581-8. doi:10.4049/jimmunol.1002241. Epub 2011 Sep 21. PubMed PMID: 21940678; PubMed Central PMCID: PMC3197947.

Honors and Awards

• Levitt Center Travel Award, February 2011
• NIH Predoctoral Immunology Training Grant, August 2009-July 2010
• NIH Predoctoral Virology Training Grant, September 2011-Present