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

被引：31

作者：

Maccari, Maria Elena ^{[1
,2
]}

Fuchs, Sebastian ^{[3
]}

Kury, Patrick ^{[1
,4
]}

Andrieux, Geoffroy ^{[5
,6
,7
]}

Volkl, Simon ^{[8
]}

Bengsch, Bertram ^{[9
,10
,11
]}

Lorenz, Myriam Ricarda ^{[12
,13
]}

Heeg, Maximilian ^{[1
,2
]}

Rohr, Jan ^{[1
,2
]}

Jagle, Sabine ^{[1
]}

Castro, Carla N. ^{[1
]}

Gross, Miriam ^{[1
]}

Warthorst, Ursula ^{[1
]}

Koenig, Christoph ^{[1
,4
]}

Fuchs, Ilka ^{[1
]}

Speckmann, Carsten ^{[1
,2
]}

Thalhammer, Julian ^{[1
,2
]}

Kapp, Friedrich G. ^{[2
]}

Seidel, Markus G. ^{[14
]}

Duckers, Gregor ^{[15
]}

Schoenberger, Stefan ^{[16
]}

Schuetz, Catharina ^{[17
]}

Fuhrer, Marita ^{[12
,13
]}

Kobbe, Robin ^{[18
]}

Holzinger, Dirk ^{[19
]}

Klemann, Christian ^{[20
]}

Smisek, Petr ^{[21
,22
]}

Owens, Stephen ^{[23
,24
]}

Horneff, Gerd ^{[25
,26
]}

Kolb, Reinhard ^{[27
]}

Naumann-Bartsch, Nora ^{[28
]}

Miano, Maurizio ^{[29
]}

Staniek, Julian ^{[4
,30
]}

Rizzi, Marta ^{[1
,30
]}

Kalina, Tomas ^{[31
,32
]}

Schneider, Pascal ^{[33
]}

Erxleben, Anika ^{[34
]}

Backofen, Rolf ^{[34
]}

Ekici, Arif ^{[35
]}

Niemeyer, Charlotte M. ^{[2
]}

Warnatz, Klaus ^{[1
]}

Grimbacher, Bodo ^{[36
,37
]}

Eibel, Hermann ^{[1
]}

Mackensen, Andreas ^{[8
]}

Frei, Andreas Philipp ^{[3
]}

Schwarz, Klaus ^{[12
,13
]}

Boerries, Melanie ^{[5
,6
,7
]}

Ehl, Stephan ^{[1
,2
,10
]}

Rensing-Ehl, Anne ^{[1
]}

机构：

[1] Univ Freiburg, Fac Med, Ctr Chron Immunodeficiency, Inst Immunodeficiency,Med Ctr, Freiburg, Germany

[2] Univ Freiburg, Fac Med, Med Ctr, Div Pediat Hematol & Oncol,Dept Pediat & Adolesce, Freiburg, Germany

[3] Roche Innovat Ctr Basel, Roche Pharma Res & Early Dev Immunol Infect Dis &, Basel, Switzerland

[4] Univ Freiburg, Fac Biol, Freiburg, Germany

[5] Univ Freiburg, Fac Med, Med Ctr, Inst Med Bioinformat & Syst Med, Freiburg, Germany

[6] German Canc Consortium, Freiburg, Germany

[7] German Canc Res Ctr, Heidelberg, Germany

[8] Univ Erlangen Nurnberg, Dept Internal Med Hematol Oncol 5, Erlangen, Germany

[9] Univ Freiburg, Fac Med, Dept Med Gastroenterol Hepatol Endocrinol & Infec, Med Ctr, Freiburg, Germany

[10] Albert Ludwigs Univ, Ctr Integrat Biological Signaling Studies, Freiburg, Germany

[11] Univ Freiburg, Bioss Ctr Biol Signalling Studies, Freiburg, Germany

[12] Univ Ulm, Inst Transfus Med, Ulm, Germany

[13] German Red Cross Blood Serv Baden Wuerttemberg He, Inst Clin Transfus Med & Immunogenet Ulm, Ulm, Germany

[14] Med Univ Graz, Dept Pediat & Adolescent Med, Div Pediat Hematol Oncol, Graz, Austria

[15] Childrens Hosp, Helios Kliniken Krefeld, Krefeld, Germany

[16] Univ Bonn, Univ Childrens Hosp Bonn, Dept Paediat Haematol & Oncol, Bonn, Germany

[17] Tech Univ Dresden, Dept Pediat, Univ Hosp Carl Gustav Carus, Dresden, Germany

[18] Univ Med Ctr Hamburg Eppendorf, Dept Med 1, Div Infect Dis, Hamburg, Germany

[19] Univ Duisburg Essen, Dept Pediat Hematol Oncol, Essen, Germany

[20] Hannover Med Sch, Dept Pediat Pulmonol Allergy & Neonatol, Hannover, Germany

[21] Univ Hosp Motol, Dept Pediat Hematol & Oncol, Prague, Czech Republic

[22] Charles Univ Prague, Fac Med 2, Prague, Czech Republic

[23] Newcastle Tyne Hosp NHS Fdn Trust, Great North Childrens Hosp, Newcastle Upon Tyne, Tyne & Wear, England

[24] Newcastle Univ, Inst Hlth & Soc, Newcastle Upon Tyne, Tyne & Wear, England

[25] Clin Sankt Augustin, Dept Gen Paediat, St Augustin, Germany

[26] Univ Hosp Cologne, Dept Pediat & Adolescent Med, Cologne, Germany

[27] Clin Oldenburg, Dept Gen Paediat, Oldenburg, Germany

[28] Friedrich Alexander Univ Erlangen Nurnberg, Dept Pediat, Erlangen, Germany

[29] Ist Ricovero & Cura Carattere Sci Ist Giannina Ga, Haematol Unit, Genoa, Italy

[30] Univ Freiburg, Fac Med, Dept Rheumatol & Clin Immunol, Med Ctr, Freiburg, Germany

[31] Charles Univ Prague, Sch Med 2, Dept Pediat Hematol & Oncol, Childhood Leukemia Invest Prague, Prague, Czech Republic

[32] Univ Hosp Motol, Prague, Czech Republic

[33] Univ Lausanne, Dept Biochem, Epalinges, Switzerland

[34] Univ Freiburg, Inst Comp Sci, Fac Engn, Bioinformat, Freiburg, Germany

[35] Univ Erlangen Nurnberg, Inst Human Genet, Erlangen, Germany

[36] Satellite Ctr, German Ctr Infect Res, Freiburg, Germany

[37] Hanover Med Sch, Satellite Ctr, Resolving Infect Susceptibil Cluster Excellence 2, Freiburg, Germany

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2021年 / 218卷 / 02期

关键词：

AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME; SYNDROME EXPRESS; APOPTOSIS; DEATH; MUTATIONS; EFFECTOR; DIFFERENTIATION; VISUALIZATION; INACTIVATION; ACTIVATION;

D O I：

10.1084/jem.20192191

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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 TCR alpha beta(+) 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.

引用

页数：25

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