Continual exit of human cutaneous resident memory CD4 T cells that seed distant skin sites

Klicznik, M. M.; Morawski, P. A.; Höllbacher, B.; Varkande, S.; Motley, S.; Rosenblum, M. D.; Duhen, T.; Campbell, D.; Gratz, I. K.

doi:10.1101/361758

bioRxiv · 10.1101/361758

Continual exit of human cutaneous resident memory CD4 T cells that seed distant skin sites

Klicznik, M. M.·Morawski, P. A.·Höllbacher, B.·Varkande, S.·Motley, S.·Rosenblum, M. D.·Duhen, T.·Campbell, D.·Gratz, I. K.

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Abstract

Tissue-resident memory T cells (TRM) persist locally in non-lymphoid tissues where they provide front-line defense against recurring insults. TRM at barrier surfaces express the markers CD103 and/or CD69 which function to retain them in epithelial tissues. In humans, neither the long-term migratory behavior of TRM nor their ability to re-enter the circulation and potentially migrate to distant tissue sites have been investigated. Using tissue explant cultures, we found that CD4+CD69+CD103+ TRM in human skin can downregulate CD69 and exit the tissue. Additionally, we identified a skin-tropic CD4+CD69-CD103+ population in human lymph and blood that is transcriptionally, functionally and clonally related to the CD4+CD69+CD103+ TRM population in the skin. Using a skin xenograft model, we confirmed that a fraction of the human cutaneous CD4+CD103+ TRM population can re-enter circulation, and migrate to secondary human skin sites where they re-assume a TRM phenotype. Thus, our data challenge current concepts regarding the strict tissue compartmentalization of CD4+ T cell memory in humans. One Sentence SummaryHuman CD4+CD103+ cutaneous resident memory T cells are found in the circulation of healthy subjects, and these cells can seed distant skin sites.

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Klicznik, M. M., Morawski, P. A., Höllbacher, B., Varkande, S., Motley, S., Rosenblum, M. D., Duhen, T., Campbell, D., Gratz, I. K.. 2018-07-03. Continual exit of human cutaneous resident memory CD4 T cells that seed distant skin sites. https://doi.org/10.1101/361758

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