Continuous T Cell Receptor Signals Maintain a Functional Regulatory T Cell Pool

J. Christoph Vahl; Christoph Drees; Klaus Heger; Sylvia Heink; Julius C. Fischer; Jelena Nedjic; Naganari Ohkura; Hiromasa Morikawa; Hendrik Poeck; Sonja Schallenberg; David Rieß; Marco Y. Hein; Thorsten Buch; Bojan Polic; Anne Schönle; Robert Zeiser; Annette Schmitt-Gräff; Karsten Kretschmer; Ludger Klein; Thomas Korn; Shimon Sakaguchi; Marc Schmidt-Supprian

doi:10.1016/j.immuni.2014.10.012

Continuous T Cell Receptor Signals Maintain a Functional Regulatory T Cell Pool

J. Christoph Vahl, Christoph Drees, Klaus Heger, Sylvia Heink, Julius C. Fischer, Jelena Nedjic, Naganari Ohkura, Hiromasa Morikawa, Hendrik Poeck, Sonja Schallenberg, David Rieß, Marco Y. Hein, Thorsten Buch, Bojan Polic, Anne Schönle, Robert Zeiser, Annette Schmitt-Gräff, Karsten Kretschmer, Ludger Klein, Thomas KornShimon Sakaguchi, Marc Schmidt-Supprian

Research output: Contribution to journal › Article › peer-review

258 Scopus citations

Abstract

Regulatory T (Treg) cells maintain immune homeostasis and prevent inflammatory and autoimmune responses. During development, thymocytes bearing a moderately self-reactive Tcell receptor (TCR) can be selected to become Treg cells. Several observations suggest that also in the periphery mature Treg cells continuously receive self-reactive TCR signals. However, the importance of this inherent autoreactivity for Treg cell biology remains poorly defined. To address this open question, we genetically ablated the TCR of mature Treg cells invivo. These experiments revealed that TCR-induced Treg lineage-defining Foxp3 expression and gene hypomethylation were uncoupled from TCR input in mature Treg cells. However, Treg cell homeostasis, cell-type-specific gene expression and suppressive function critically depend on continuous triggering of their TCR.

Original language	English
Pages (from-to)	722-736
Number of pages	15
Journal	Immunity
Volume	41
Issue number	5
DOIs	https://doi.org/10.1016/j.immuni.2014.10.012
State	Published - 20 Nov 2014

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Vahl, J. C., Drees, C., Heger, K., Heink, S., Fischer, J. C., Nedjic, J., Ohkura, N., Morikawa, H., Poeck, H., Schallenberg, S., Rieß, D., Hein, M. Y., Buch, T., Polic, B., Schönle, A., Zeiser, R., Schmitt-Gräff, A., Kretschmer, K., Klein, L., ... Schmidt-Supprian, M. (2014). Continuous T Cell Receptor Signals Maintain a Functional Regulatory T Cell Pool. Immunity, 41(5), 722-736. https://doi.org/10.1016/j.immuni.2014.10.012

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title = "Continuous T Cell Receptor Signals Maintain a Functional Regulatory T Cell Pool",

abstract = "Regulatory T (Treg) cells maintain immune homeostasis and prevent inflammatory and autoimmune responses. During development, thymocytes bearing a moderately self-reactive Tcell receptor (TCR) can be selected to become Treg cells. Several observations suggest that also in the periphery mature Treg cells continuously receive self-reactive TCR signals. However, the importance of this inherent autoreactivity for Treg cell biology remains poorly defined. To address this open question, we genetically ablated the TCR of mature Treg cells invivo. These experiments revealed that TCR-induced Treg lineage-defining Foxp3 expression and gene hypomethylation were uncoupled from TCR input in mature Treg cells. However, Treg cell homeostasis, cell-type-specific gene expression and suppressive function critically depend on continuous triggering of their TCR.",

author = "Vahl, \{J. Christoph\} and Christoph Drees and Klaus Heger and Sylvia Heink and Fischer, \{Julius C.\} and Jelena Nedjic and Naganari Ohkura and Hiromasa Morikawa and Hendrik Poeck and Sonja Schallenberg and David Rie{\ss} and Hein, \{Marco Y.\} and Thorsten Buch and Bojan Polic and Anne Sch{\"o}nle and Robert Zeiser and Annette Schmitt-Gr{\"a}ff and Karsten Kretschmer and Ludger Klein and Thomas Korn and Shimon Sakaguchi and Marc Schmidt-Supprian",

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month = nov,

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doi = "10.1016/j.immuni.2014.10.012",

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Vahl, JC, Drees, C, Heger, K, Heink, S, Fischer, JC, Nedjic, J, Ohkura, N, Morikawa, H, Poeck, H, Schallenberg, S, Rieß, D, Hein, MY, Buch, T, Polic, B, Schönle, A, Zeiser, R, Schmitt-Gräff, A, Kretschmer, K, Klein, L, Korn, T, Sakaguchi, S & Schmidt-Supprian, M 2014, 'Continuous T Cell Receptor Signals Maintain a Functional Regulatory T Cell Pool', Immunity, vol. 41, no. 5, pp. 722-736. https://doi.org/10.1016/j.immuni.2014.10.012

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T1 - Continuous T Cell Receptor Signals Maintain a Functional Regulatory T Cell Pool

AU - Vahl, J. Christoph

AU - Drees, Christoph

AU - Heger, Klaus

AU - Heink, Sylvia

AU - Fischer, Julius C.

AU - Nedjic, Jelena

AU - Ohkura, Naganari

AU - Morikawa, Hiromasa

AU - Poeck, Hendrik

AU - Schallenberg, Sonja

AU - Rieß, David

AU - Hein, Marco Y.

AU - Buch, Thorsten

AU - Polic, Bojan

AU - Schönle, Anne

AU - Zeiser, Robert

AU - Schmitt-Gräff, Annette

AU - Kretschmer, Karsten

AU - Klein, Ludger

AU - Korn, Thomas

AU - Sakaguchi, Shimon

AU - Schmidt-Supprian, Marc

PY - 2014/11/20

Y1 - 2014/11/20

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AB - Regulatory T (Treg) cells maintain immune homeostasis and prevent inflammatory and autoimmune responses. During development, thymocytes bearing a moderately self-reactive Tcell receptor (TCR) can be selected to become Treg cells. Several observations suggest that also in the periphery mature Treg cells continuously receive self-reactive TCR signals. However, the importance of this inherent autoreactivity for Treg cell biology remains poorly defined. To address this open question, we genetically ablated the TCR of mature Treg cells invivo. These experiments revealed that TCR-induced Treg lineage-defining Foxp3 expression and gene hypomethylation were uncoupled from TCR input in mature Treg cells. However, Treg cell homeostasis, cell-type-specific gene expression and suppressive function critically depend on continuous triggering of their TCR.

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JO - Immunity

JF - Immunity

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ER -

Continuous T Cell Receptor Signals Maintain a Functional Regulatory T Cell Pool

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