Molecular and functional characterizations of memory CD8 T cell populations

CD8 T cells are specialized cells of the immune system that play an essential role in the control of infection and in tumor immuno-surveillance. A unique characteristic of CD8 T cell responses is that they are able to provide enhanced protection when encountering a pathogen for a second time, a phenomenon called immunological memory. It has been shown that memory CD8 T cells are maintained for the life of the laboratory mouse and for great lengths of time (up to 75 years) in human individuals. However, changes that occur within the memory population over time have been incompletely characterized. My work in the Badovinac laboratory is aimed at characterizing the changes that occur in the memory population over time after infection or vaccination. I am currently employing a number of techniques to explore this question including analysis of transcriptional and functional changes; including changes in phenotype that occur in memory populations over time. These studies have important implications in human health and immune system function, as it is possible that CD8 T cells may not re-encounter their cognate antigen for many years after vaccination or initial infection. Additionally, this work will provide knowledge of the differentiation process that occurs in memory CD8 T cells after infection or vaccination.

Martin MD, Badovinac VP. Defining Memory CD8 T Cell. Front Immunol. 2018 Nov 20;9:2692. doi: 10.3389/fimmu.2018.02692. eCollection 2018. Review. PubMed PMID: 30515169; PubMed Central PMCID: PMC6255921.

Martin MD, Danahy DB, Hartwig SM, Harty JT, Badovinac VP. Revealing theComplexity in CD8 T Cell Responses to Infection in Inbred C57B/6 versus Outbred Swiss Mice. Front Immunol. 2017 Nov 22;8:1527. doi: 10.3389/fimmu.2017.01527.eCollection 2017. PubMed PMID: 29213267; PubMed Central PMCID: PMC5702636.

Martin MD, Shan Q, Xue HH, Badovinac VP. Time and Antigen-Stimulation History Influence Memory CD8 T Cell Bystander Responses. Front Immunol. 2017 Jun 8;8:634. doi: 10.3389/fimmu.2017.00634. eCollection 2017. PubMed PMID: 28642758; PubMed Central PMCID: PMC5462920.

Shan Q, Zeng Z, Xing S, Li F, Hartwig SM, Gullicksrud JA, Kurup SP, Van Braeckel-Budimir N, Su Y, Martin MD, Varga SM, Taniuchi I, Harty JT, Peng W, Badovinac VP, Xue HH. The transcription factor Runx3 guards cytotoxic CD8(+) effector T cells against deviation towards follicular helper T cell lineage. Nat Immunol. 2017 Aug;18(8):931-939. doi: 10.1038/ni.3773. Epub 2017 Jun 12. PubMed PMID: 28604718; PubMed Central PMCID: PMC5564218.

Van Braeckel-Budimir N, Martin MD, Hartwig SM, Legge KL, Badovinac VP, Harty JT. Antigen Exposure History Defines CD8 T Cell Dynamics and Protection during Localized Pulmonary Infections. Front Immunol. 2017 Jan 27;8:40. doi:10.3389/fimmu.2017.00040. PubMed PMID: 28191007; PubMed Central PMCID:PMC5269565.

Martin MD, Badovinac VP. Sifting through CD8(+) T Cell Memory. Immunity. 2016 Dec 20;45(6):1184-1186. doi: 10.1016/j.immuni.2016.12.005. PubMed PMID: 28002725.

He B, Xing S, Chen C, Gao P, Teng L, Shan Q, Gullicksrud JA, Martin MD, Yu S, Harty JT, Badovinac VP, Tan K, Xue HH. CD8(+) T Cells Utilize Highly Dynamic Enhancer Repertoires and Regulatory Circuitry in Response to Infections. Immunity. 2016 Dec 20;45(6):1341-1354. doi: 10.1016/j.immuni.2016.11.009. PubMed PMID: 27986453; PubMed Central PMCID:PMC5304416.

Janowski AM, Colegio OR, Hornick EE, McNiff JM, Martin MD, Badovinac VP, Norian LA, Zhang W, Cassel SL, Sutterwala FS. NLRC4 suppresses melanoma tumor progression independently of inflammasome activation. J Clin Invest. 2016 Oct 3;126(10):3917-3928. doi: 10.1172/JCI86953. PubMed PMID: 27617861; PubMed Central PMCID: PMC5096827.

Martin MD, Badovinac VP. Antigen-dependent and -independent contributions to primary memory CD8 T cell activation and protection following infection. Sci Rep. 2015 Dec 10;5:18022. doi: 10.1038/srep18022. PubMed PMID: 26658291; PubMed Central PMCID: PMC4675085.

Martin MD, Kim MT, Shan Q, Sompallae R, Xue HH, Harty JT, Badovinac VP. Phenotypic and Functional Alterations in Circulating Memory CD8 T Cells with Time after Primary Infection. PLoS Pathog. 2015 Oct 20;11(10):e1005219. doi:10.1371/journal.ppat.1005219. PubMed PMID: 26485703; PubMed Central PMCID:PMC4618693.

Khan SH, Martin MD, Starbeck-Miller GR, Xue HH, Harty JT, Badovinac VP. The Timing of Stimulation and IL-2 Signaling Regulate Secondary CD8 T Cell Responses. PLoS Pathog. 2015 Oct 2;11(10):e1005199. doi: 10.1371/journal.ppat.1005199. PubMed PMID: 26431533; PubMed Central PMCID: PMC4592272.

Rai D, Martin MD, Badovinac VP. The Longevity of Memory CD8 T Cell Responses after Repetitive Antigen Stimulations. J Immunol. 2014 Jun 15;192(12):5652-5659. Epub 2014 May 14. PubMed PMID: 24829415.

Martin MD, Badovinac VP. Influence of time and number of antigen encounters on memory CD8 T cell development. Immunol Res. 2014 May 14. [Epub ahead of print] PubMed PMID: 24825776.

Duong S, Condotta SA, Rai D, Martin MD, Griffith TS, Badovinac VP. Polymicrobial sepsis alters antigen-dependent and -independent memory CD8 T cell functions. J Immunol. 2014 Apr 15;192(8):3618-25. doi: 10.4049/jimmunol.1303460. Epub 2014 Mar 19. PubMed PMID: 24646738; PubMed Central PMCID: PMC4001259.

Martin MD, Condotta SA, Harty JT, Badovinac VP. Population dynamics of naïve and memory CD8 T cell responses after antigen stimulations in vivo. J Immunol. 2012 Feb 1;188(3):1255-65. doi: 10.4049/jimmunol.1101579. Epub 2011 Dec 28. PubMed PMID: 22205031; PubMed Central PMCID: PMC3262935.

Wirth TC, Martin MD, Starbeck-Miller G, Harty JT, Badovinac VP. Secondary CD8+ T-cell responses are controlled by systemic inflammation. Eur J Immunol. 2011 May;41(5):1321-33. doi: 10.1002/eji.201040730. Epub 2011 Mar 21. PubMed PMID:21425157; PubMed Central PMCID: PMC3083480.

Martin MD, Wirth TC, Lauer P, Harty JT, Badovinac VP. The impact of pre-existing memory on differentiation of newly recruited naive CD8 T cells. J Immunol. 2011 Sep 15;187(6):2923-31. doi: 10.4049/jimmunol.1100698. Epub 2011 Aug 10. PubMed PMID: 21832161; PubMed Central PMCID: PMC3169750.