Naive T cells give rise equally to TCR-identical T-RM and T-CM after skin antigen exposure

Publication Type:

Journal Article


Journal of Investigative Dermatology, Volume 134, p.S6-S6 (2014)


2014, Human Biology Division, Human Biology Division Public Health Sciences Division May 2014 2014Q2 CCSG, May 2014, Public Health Sciences Division


T cell immune memory resides in different anatomic compartments such as lymph nodes (LN), in the form of central memory T cells (TCM), and peripheral tissues, as resident memory T cells (TRM). We studied the relationship between these two subsets of memory T cells generated after antigen encounter in a model barrier tissue: skin. Instead of employing transgenic mice whose T cells have only a single αβ T cell receptor (TCR), we used a powerful new tool —high-throughput sequencing of TCR’s— to track many thousands of T cells between tissue samples. We tested three diverse antigenic challenges broadly relevant to human disease—a chemical hapten, a protein, and a virus—and used wild-type mice to observe in vivo immune responses. Here we show that during the memory phase of the immune response (>35d), for every expanded skin TRM clone, there exists a TCM clone in LN with an identical TCR, and that these TCR-identical clones are present in similar numbers. This indicates common origin from a single naive T cell, but these sequencing data further suggest that the TCR repertoire of TRM in tissue—and thus their antigen specificity— is mirrored by TCM in LN. Though after a simple immunization, these skin TRM and corresponding LN TCM clones are present in similar numbers, repetitive antigen exposure to skin expanded skin TRM clones preferentially over their TCR-identical TCM counterparts. Our results show that murine contact hypersensitivity (CHS), the counterpart of human allergic contact dermatitis, is a TRM-mediated disease and does not require circulating T cells. However, TCM can give rise to skin TRM after hapten re-exposure. We speculate that TRM are designed evolutionarily to allow for rapid local responses to pathogens, but that their activities are subverted in several chronic human diseases affecting barrier tissues.


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