The in vivo dynamics of memory CD8 T cells

My research interests lie in understanding the in vivo dynamics of memory CD8 T cells. Memory CD8 T cells play an important role in mediating protective immunity against intracellular pathogens. The dynamic processes occurring within the memory CD8 T cell population over time involve a complex combination of subset differentiation and maintenance. Although basic CD8 T cell kinetics of expansion, contraction, and memory maintenance in response to infection and vaccination have been described, mechanisms regulating their numbers and subset differentiation are not well defined.

There are 2 main features of memory CD8 T cells: maintenance of stable numbers over time and changes in subset representation from predominantly T Effector Memory (TEM) into predominantly T Central Memory (TCM), each possessing distinct characteristics to enhance host protection. The current paradigm of memory CD8 T cell maintenance is based on a model of IL-15-driven homeostatic proliferation. However, several studies suggest the possibility for IL-15-independent mechanisms of memory maintenance. I am investigating other signals that may maintain numeric stability of the memory CD8 T cell compartment. In addition to total numbers, the unique characteristics of memory subsets provide the other component to superior CD8 memory T cell-mediated protection. Depending on the nature of the pathogen, TEM or TCM may provide better protection to the host. Thus, I am also studying the mechanism by which memory CD8 T cell subsets differentiate from TEM to TCM.

Kim MT, Richer MJ, Gross BP, Norian LA, Badovinac VP, Harty JT. Enhancing Dendritic Cell-based Immunotherapy with IL-2/Monoclonal Antibody Complexes for Control of Established Tumors. J Immunol. 2015 Nov 1;195(9):4537-44. doi:10.4049/jimmunol.1501071. PubMed PMID: 26408669; PubMed Central PMCID:PMC4610867.

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.

Kim MT, Kurup SP, Starbeck-Miller GR, Harty JT. Manipulating Memory CD8 T Cell Numbers by Timed Enhancement of IL-2 Signals. J Immunol. 2016 Sep 1;197(5):1754-61. doi: 10.4049/jimmunol.1600641. PubMed PMID: 27439516; PubMed Central PMCID: PMC4992593.

Kim MT, Harty JT. Splenectomy Alters Distribution and Turnover but not Numbers or Protective Capacity of de novo Generated Memory CD8 T-Cells. Front Immunol. 2014 Nov 6;5:568. doi: 10.3389/fimmu.2014.00568. eCollection 2014. PubMed PMID:25414706; PubMed Central PMCID: PMC4222231.

Kim MT, Harty JT. Impact of Inflammatory Cytokines on Effector and Memory CD8+ T Cells. Front Immunol. 2014 Jun 19;5:295. doi: 10.3389/fimmu.2014.00295. eCollection 2014. Review. PubMed PMID: 24995011; PubMed Central PMCID:PMC4062963.