TGF-β signalling is required for CD4⁺ T cell homeostasis but dispensable for regulatory T cell function.
TGF-β is widely held to be critical for the maintenance and function of regulatory T (T(reg)) cells and thus peripheral tolerance. This is highlighted by constitutive ablation of TGF-β receptor (TR) during thymic development in mice, which leads to a lethal autoimmune syndrome. Here we describe that...
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2013
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oai:doaj.org-article:9efc6ada7857426e844de069ad67186a2021-11-18T05:37:48ZTGF-β signalling is required for CD4⁺ T cell homeostasis but dispensable for regulatory T cell function.1544-91731545-788510.1371/journal.pbio.1001674https://doaj.org/article/9efc6ada7857426e844de069ad67186a2013-10-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24115907/?tool=EBIhttps://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885TGF-β is widely held to be critical for the maintenance and function of regulatory T (T(reg)) cells and thus peripheral tolerance. This is highlighted by constitutive ablation of TGF-β receptor (TR) during thymic development in mice, which leads to a lethal autoimmune syndrome. Here we describe that TGF-β-driven peripheral tolerance is not regulated by TGF-β signalling on mature CD4⁺ T cells. Inducible TR2 ablation specifically on CD4⁺ T cells did not result in a lethal autoinflammation. Transfer of these TR2-deficient CD4⁺ T cells to lymphopenic recipients resulted in colitis, but not overt autoimmunity. In contrast, thymic ablation of TR2 in combination with lymphopenia led to lethal multi-organ inflammation. Interestingly, deletion of TR2 on mature CD4⁺ T cells does not result in the collapse of the T(reg) cell population as observed in constitutive models. Instead, a pronounced enlargement of both regulatory and effector memory T cell pools was observed. This expansion is cell-intrinsic and seems to be caused by increased T cell receptor sensitivity independently of common gamma chain-dependent cytokine signals. The expression of Foxp3 and other regulatory T cells markers was not dependent on TGF-β signalling and the TR2-deficient T(reg) cells retained their suppressive function both in vitro and in vivo. In summary, absence of TGF-β signalling on mature CD4⁺ T cells is not responsible for breakdown of peripheral tolerance, but rather controls homeostasis of mature T cells in adult mice.Anna SledzińskaSaskia HemmersFlorian MairOliver GorkaJürgen RulandLynsey FairbairnAnja NisslerWerner MüllerAri WaismanBurkhard BecherThorsten BuchPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 11, Iss 10, p e1001674 (2013) |
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DOAJ |
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| topic |
Biology (General) QH301-705.5 |
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Biology (General) QH301-705.5 Anna Sledzińska Saskia Hemmers Florian Mair Oliver Gorka Jürgen Ruland Lynsey Fairbairn Anja Nissler Werner Müller Ari Waisman Burkhard Becher Thorsten Buch TGF-β signalling is required for CD4⁺ T cell homeostasis but dispensable for regulatory T cell function. |
| description |
TGF-β is widely held to be critical for the maintenance and function of regulatory T (T(reg)) cells and thus peripheral tolerance. This is highlighted by constitutive ablation of TGF-β receptor (TR) during thymic development in mice, which leads to a lethal autoimmune syndrome. Here we describe that TGF-β-driven peripheral tolerance is not regulated by TGF-β signalling on mature CD4⁺ T cells. Inducible TR2 ablation specifically on CD4⁺ T cells did not result in a lethal autoinflammation. Transfer of these TR2-deficient CD4⁺ T cells to lymphopenic recipients resulted in colitis, but not overt autoimmunity. In contrast, thymic ablation of TR2 in combination with lymphopenia led to lethal multi-organ inflammation. Interestingly, deletion of TR2 on mature CD4⁺ T cells does not result in the collapse of the T(reg) cell population as observed in constitutive models. Instead, a pronounced enlargement of both regulatory and effector memory T cell pools was observed. This expansion is cell-intrinsic and seems to be caused by increased T cell receptor sensitivity independently of common gamma chain-dependent cytokine signals. The expression of Foxp3 and other regulatory T cells markers was not dependent on TGF-β signalling and the TR2-deficient T(reg) cells retained their suppressive function both in vitro and in vivo. In summary, absence of TGF-β signalling on mature CD4⁺ T cells is not responsible for breakdown of peripheral tolerance, but rather controls homeostasis of mature T cells in adult mice. |
| format |
article |
| author |
Anna Sledzińska Saskia Hemmers Florian Mair Oliver Gorka Jürgen Ruland Lynsey Fairbairn Anja Nissler Werner Müller Ari Waisman Burkhard Becher Thorsten Buch |
| author_facet |
Anna Sledzińska Saskia Hemmers Florian Mair Oliver Gorka Jürgen Ruland Lynsey Fairbairn Anja Nissler Werner Müller Ari Waisman Burkhard Becher Thorsten Buch |
| author_sort |
Anna Sledzińska |
| title |
TGF-β signalling is required for CD4⁺ T cell homeostasis but dispensable for regulatory T cell function. |
| title_short |
TGF-β signalling is required for CD4⁺ T cell homeostasis but dispensable for regulatory T cell function. |
| title_full |
TGF-β signalling is required for CD4⁺ T cell homeostasis but dispensable for regulatory T cell function. |
| title_fullStr |
TGF-β signalling is required for CD4⁺ T cell homeostasis but dispensable for regulatory T cell function. |
| title_full_unstemmed |
TGF-β signalling is required for CD4⁺ T cell homeostasis but dispensable for regulatory T cell function. |
| title_sort |
tgf-β signalling is required for cd4⁺ t cell homeostasis but dispensable for regulatory t cell function. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/9efc6ada7857426e844de069ad67186a |
| work_keys_str_mv |
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