The human tissue-resident CCR5+ T cell compartment maintains protective and functional properties during inflammation

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Science Translational Medicine  04 Dec 2019:
Vol. 11, Issue 521, eaaw8718
DOI: 10.1126/scitranslmed.aaw8718

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Tissue-resident T cells evade eviction

CCR5 antagonism, explored in various disease settings, does not appear to disrupt barrier immunity. Woodward Davis et al. examined human oral mucosa to characterize CCR5+ T cells in healthy and inflamed tissues. These cells were present below the epithelia and accumulated during inflammation. They had a range of phenotypes, including TH1, TH17, and regulatory cells. Rectal biopsies from a clinical trial using a CCR5 antagonist revealed that CCR5+ T cells were retained even during treatment. These data show that tissue residency may not be perturbed by CCR5 antagonism, allowing barrier immunity to remain intact.


CCR5 is thought to play a central role in orchestrating migration of cells in response to inflammation. CCR5 antagonists can reduce inflammatory disease processes, which has led to an increased interest in using CCR5 antagonists in a wide range of inflammation-driven diseases. Paradoxically, these antagonists appear to function without negatively affecting host immunity at barrier sites. We reasoned that the resolution to this paradox may lie in the CCR5+ T cell populations that permanently reside in tissues. We used a single-cell analysis approach to examine the human CCR5+ T cell compartment in the blood, healthy, and inflamed mucosal tissues to resolve these seemingly contradictory observations. We found that 65% of the CD4 tissue-resident memory T (TRM) cell compartment expressed CCR5. These CCR5+ TRM cells were enriched in and near the epithelial layer and not only limited to TH1-type cells but also contained a large TH17-producing and a stable regulatory T cell population. The CCR5+ TRM compartment was stably maintained even in inflamed tissues including the preservation of TH17 and regulatory T cell populations. Further, using tissues from the CHARM-03 clinical trial, we found that CCR5+ TRM are preserved in human mucosal tissue during treatment with the CCR5 antagonist Maraviroc. Our data suggest that the human CCR5+ TRM compartment is functionally and spatially equipped to maintain barrier immunity even in the absence of CCR5-mediated, de novo T cell recruitment from the periphery.

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