A distinct CD38+CD45RA+ population of CD4+, CD8+, and double-negative T cells is controlled by FAS

Maccari ME, Fuchs S, Kury P, Andrieux G, Bengsch B, Lorenz MR, Heeg M, Rohr J, Jägle S, Castro CN, Groß M, Warthorst U, König C, Fuchs I, Speckmann C, Thalhammer J, Kapp FG, Seidel MG, Dückers G, Schönberger S, Schütz C, Führer M, Kobbe R, Holzinger D, Klemann C, Smisek P, Owens S, Horneff G, Kolb R, Naumann-Bartsch N, Miano M, Staniek J, Rizzi M, Kalina T, Schneider P, Erxleben A, Backofen R, Ekici AB, Niemeyer CM, Warnatz K, Grimbacher B, Eibel H, Mackensen A, Frei AP, Schwarz K, Boerries M, Ehl S, Rensing-Ehl A, Völkl S (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Journal of Experimental Medicine Rockefeller University Press

Book Volume: 218

Journal Issue: 2

DOI: 10.1084/jem.20192191

Abstract

The identification and characterization of rare immune cell populations in humans can be facilitated by their growth advantage in the context of specific genetic diseases. Here, we use autoimmune lymphoproliferative syndrome to identify a population of FAS-controlled TCRαβ+ T cells. They include CD4+, CD8+, and double-negative T cells and can be defined by a CD38+CD45RA+T-BET- expression pattern. These unconventional T cells are present in healthy individuals, are generated before birth, are enriched in lymphoid tissue, and do not expand during acute viral infection. They are characterized by a unique molecular signature that is unambiguously different from other known T cell differentiation subsets and independent of CD4 or CD8 expression. Functionally, FAS-controlled T cells represent highly proliferative, noncytotoxic T cells with an IL-10 cytokine bias. Mechanistically, regulation of this physiological population is mediated by FAS and CTLA4 signaling, and its survival is enhanced by mTOR and STAT3 signals. Genetic alterations in these pathways result in expansion of FAS-controlled T cells, which can cause significant lymphoproliferative disease.

Authors with CRIS profile

Arif Bülent Ekici Institute of Human Genetics Andreas Mackensen Lehrstuhl für Innere Medizin V Simon Völkl Department of Medicine 5 – Haematology and Oncology

Involved external institutions

Albert-Ludwigs-Universität Freiburg DE Germany (DE) Newcastle upon Tyne Hospitals NHS Foundation Trust GB United Kingdom (GB) Motol University Hospital / Fakultní nemocnice v Motole CZ Czech Republic (CZ) Istituto Giannina Gaslini IT Italy (IT) Universität Ulm DE Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) DE Germany (DE) Universität Duisburg-Essen (UDE) DE Germany (DE) HELIOS Kliniken DE Germany (DE) Universitätsklinikum Carl Gustav Carus Dresden DE Germany (DE) Klinikum Oldenburg DE Germany (DE) Université de Lausanne (UNIL) CH Switzerland (CH) F. Hoffmann-La Roche Ltd CH Switzerland (CH) Medizinische Universität Graz AT Austria (AT) Medizinische Hochschule Hannover (MHH) / Hannover Medical School DE Germany (DE) Universitätsklinikum Bonn DE Germany (DE)

How to cite

APA:

Maccari, M.E., Fuchs, S., Kury, P., Andrieux, G., Bengsch, B., Lorenz, M.R.,... Völkl, S. (2021). A distinct CD38+CD45RA+ population of CD4+, CD8+, and double-negative T cells is controlled by FAS. Journal of Experimental Medicine, 218(2). https://doi.org/10.1084/jem.20192191

MLA:

Maccari, Maria Elena, et al. "A distinct CD38+CD45RA+ population of CD4+, CD8+, and double-negative T cells is controlled by FAS." Journal of Experimental Medicine 218.2 (2021).

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