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CD8+/CD103+ tissue-resident memory T cells display substantial functional plasticity and fine-tune their phenotype to meet local needs

Lupsa, Nikolett and Érsek, Barbara and Pócza, Péter and Sarzsinszky, Eszter and Toth, Anett and Bagita, Bence and Bencsik, András and Hegyesi, Hargita and Matolcsy, András and Buzás, Edit Irén and Pós, Zoltán (2015) CD8+/CD103+ tissue-resident memory T cells display substantial functional plasticity and fine-tune their phenotype to meet local needs. Journal of Molecular Cell Biology. (Submitted)

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Abstract

n this study we sought a better understanding of t he unique phenotypic plasticity displayed by CD8+/CD103+ tissue-resident memory T cells (Trms ) in distinct tissue environments. Murine Trm cells were isolated from distinct tissues by automa ted tissue dissociation and magnetic sorting. Distinctive features of the Trm phenotype in distin ct tissues were described by microarray gene expression profiling, Q-PCR, UPLC-MS/MS, and flow c ytometry. We found that CD8+ small intestinal Trms frequently exhibit an effector-like phenotype, express various chemokines, granzymes A/B, show evi dence of degranulation, intense protein synthesis and sustained clonal expansion. In contra st, lung-resident Trms typically express lymphotoxins α/β, but not granzymes or markers of degranulation, and rarely divide due to G2/M arrest. Finally, CD8+ CD103+ T cells in the liver, a tolerogenic environment for CD8+ T cells, are mostly dormant, but often positive for CXCR4, a rec eptor of the liver-released chemokine SDF-1. We also found, however, that subtle phenotypic changes affect non-resident CD8+ T effector (Teff) cells infiltrating the same tissues, too. Although far le ss pronounced, these changes were often analogous to those observed in Trm cells. These data suggest that Trm cells display a unique phenotypic plasticity and adapt to varying environmental conditions by multiple, although not exclusively Trm-restricted mechanisms.

Item Type: Article
Subjects: Q Science / természettudomány > Q1 Science (General) / természettudomány általában
R Medicine / orvostudomány > R1 Medicine (General) / orvostudomány általában
Depositing User: Zoltán Pós
Date Deposited: 21 Jul 2015 17:50
Last Modified: 12 Aug 2015 19:02
URI: http://real.mtak.hu/id/eprint/25488

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