@article{4560d7863b444a4592c5cf45c8e02c48,
title = "Human antimicrobial cytotoxic T lymphocytes, defined by NK receptors and antimicrobial proteins, kill intracellular bacteria",
abstract = "Human CD8+ cytotoxic T lymphocytes (CTLs) contribute to antimicrobial defense against intracellular pathogens through secretion of cytotoxic granule proteins granzyme B, perforin, and granulysin. However, CTLs are heterogeneous in the expression of these proteins, and the subset(s) responsible for antimicrobial activity is unclear. Studying human leprosy, we found that the subset of CTLs coexpressing all three cytotoxic molecules is increased in the resistant form of the disease, can be expanded by interleukin-15 (IL-15), and is differentiated from na{\"i}ve CD8+ T cells by Langerhans cells. RNA sequencing analysis identified that these CTLs express a gene signature that includes an array of surface receptors typically expressed by natural killer (NK) cells. We determined that CD8+ CTLs expressing granzyme B, perforin, and granulysin, as well as the activating NK receptor NKG2C, represent a population of “antimicrobial CTLs” (amCTLs) capable of T cell receptor (TCR)–dependent and TCR-independent release of cytotoxic granule proteins that mediate antimicrobial activity.",
author = "Balin, {Samuel J.} and Matteo Pellegrini and Eynav Klechevsky and Won, {Sohui T.} and Weiss, {David I.} and Choi, {Aaron W.} and Joshua Hakimian and Jing Lu and Ochoa, {Maria Teresa} and Bloom, {Barry R.} and Lanier, {Lewis L.} and Steffen Stenger and Modlin, {Robert L.}",
note = "Funding Information: We would like to thank G. Chen, S. Aliyari, and M. Chapon for sharing resources; P. Liu and R. Teles for assistance with statistical analysis and helpful discussion; A. Legaspi for tissue culture assistance; D. Korenfield for technical assistance; M. Schibler and the UCLA, California NanoSystems Institute, Advanced Light Microscopy Core Facility for assistance with the confocal studies; and I. Schmid and the UCLA Jonsson Comprehensive Cancer Center and Center for AIDS Research Flow Cytometry Core Facility for assistance with flow cytometry and cell sorting. Funding: This work was supported by Dermatology Foundation grants 20151604 and 20141510 (S.J.B.); NIH grants R01HL119068, R01AI022553, R01HL129887, R01AR040312, and P50AR063020 (R.L.M.); grant AI068129; and the Parker Institute for Cancer Immunotherapy (L.L.L.). Publisher Copyright: Copyright {\textcopyright} 2018 The Authors, some rights reserved.",
year = "2018",
doi = "10.1126/sciimmunol.aat7668",
language = "English",
volume = "3",
journal = "Science Immunology",
issn = "2470-9468",
number = "26",
}