Open AccessA distinct CD38+CD45RA+ population of CD4+, CD8+, and double-negative T cells is controlled by FAS
Author(s) -
Maria Elena Maccari,
Sebastian Fuchs,
Patrick Küry,
Geoffroy Andrieux,
Simon Völkl,
Bertram Bengsch,
Myriam Ricarda Lorenz,
Maximilian Heeg,
Jan Rohr,
Sabine Jägle,
Carla Castro,
Miriam Groß,
Ursula Warthorst,
Christoph König,
Ilka Fuchs,
Carsten Speckmann,
Julian Thalhammer,
Friedrich Kapp,
Markus G. Seidel,
Gregor Dückers,
Stefan Schönberger,
Christian Schütz,
Marita Führer,
Robin Kobbe,
Dirk Holzinger,
Christian Klemann,
Petr Smíšek,
Stephen Owens,
Gerd Horneff,
R Kolb,
Nora NaumannBartsch,
Maurizio Miano,
Julian Staniek,
Marta Rizzi,
Tomáš Kalina,
Pascal Schneider,
Anika Erxleben,
Rolf Backofen,
Arif B. Ekici,
Charlotte M. Niemeyer,
Klaus Warnatz,
Bodo Grimbacher,
Hermann Eibel,
Andréas Mackensen,
Andreas P. Frei,
Klaus Schwarz,
Melanie Boerries,
Stephan Ehl,
Anne RensingEhl
Publication year - 2020
Publication title -
the journal of experimental medicine/the journal of experimental medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.483
H-Index - 448
eISSN - 1540-9538
pISSN - 0022-1007
DOI - 10.1084/jem.20192191
Subject(s) - biology , cd38 , cd8 , cytotoxic t cell , fas ligand , population , immunology , t cell , immune system , interleukin 21 , zap70 , microbiology and biotechnology , context (archaeology) , apoptosis , genetics , programmed cell death , stem cell , medicine , in vitro , paleontology , environmental health , cd34
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.