Immunity & infection
Resident memory T cells (TRM) have been identified in mouse models as having rapid protective capacities to site-specific pathogens and are key targets for vaccine-mediated protection. TRM-phenotype cells are detected in human tissues but defining characteristics of human TRM for CD4 and CD8 T cells including how TRM differ from circulatory subsets and potential mechanisms for site-specific targeting are not defined. We performed whole transcriptome profiling of memory T cell subsets from the lung, spleen and blood of 3 donors, for both CD4 and CD8 subsets, as well as in-depth phenotypic and functional profiling of memory T cells from 63 additional donors. Our results show that TRM are a transcriptionally distinct memory T cell subset in humans that can be identified by CD69 expression. We identify 30 core genes that define human TRM including the adhesion markers ITGA1 and ITGAE and homing receptors CXCR6 and CX3CR1, and we confirmed the surface expression of these genes and others by flow cytometry. TRM upregulated several cytokines transcriptionally and had a superior ability to produce IL-2, IL-17, and IFNg during stimulations compared with circulatory memory T cells. Interestingly, TRM showed enrichment of cell cycle inhibition pathways, a result which was supported by reduced Ki67 expression in TRM. TRM also upregulated IL-10, DUSP6, and PD-1, together suggesting that TRM may exist in an inhibited state to prevent inflammation-mediated tissue damage. Overall, our data comprehensively characterize CD4 and CD8 human TRM and provide new insights into how TRM establish residency and mediate protection in humans.
Professor of Surgical Sciences and Microbiology and Immunology
Donna L. Farber, Ph.D.: Brief Bio
Dr. Farber received her undergraduate degree in Microbiology from the University of Michigan, her Ph.D. in Biochemistry and Molecular Biology at the University of California, and did postdoctoral training in the Section of Immunobiology at Yale University and at the Pasteur Institute in Paris, France. She started her laboratory at the University of Maryland, Baltimore and moved to Columbia University in 2010 where she is currently a Professor of Surgical Sciences and Microbiology and Immunology. Dr. Farber’s research for the past 20 years is focused on immunological memory and recently, on how the immune response is compartmentalized in tissue sites in mouse infection models and in humans. For human studies, Dr. Farber set up a unique resource to obtain multiple tissues from organ donors, enabling novel investigation of human immunity throughout the body over age and genetic diversity.