Human antimicrobial cytotoxic T lymphocytes, defined by NK receptors and antimicrobial proteins, kill intracellular bacteria

Samuel J. Balin, Matteo Pellegrini, Eynav Klechevsky, Sohui T. Won, David I. Weiss, Aaron W. Choi, Joshua Hakimian, Jing Lu, Maria Teresa Ochoa, Barry R. Bloom, Lewis L. Lanier, Steffen Stenger, Robert L. Modlin

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12 Scopus citations

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 naïve 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.

Original languageEnglish
Article numbereaat7668
JournalScience immunology
Volume3
Issue number26
DOIs
StatePublished - Jan 1 2018

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    Balin, S. J., Pellegrini, M., Klechevsky, E., Won, S. T., Weiss, D. I., Choi, A. W., Hakimian, J., Lu, J., Ochoa, M. T., Bloom, B. R., Lanier, L. L., Stenger, S., & Modlin, R. L. (2018). Human antimicrobial cytotoxic T lymphocytes, defined by NK receptors and antimicrobial proteins, kill intracellular bacteria. Science immunology, 3(26), [eaat7668]. https://doi.org/10.1126/sciimmunol.aat7668