Interleukins 7 and 15 Maintain Human T Cell Proliferative Capacity through STAT5 Signaling

T lymphocytes require signals from self-peptides and cytokines, most notably interleukins 7 and 15 (IL-7, IL-15), for survival. While mouse T cells die rapidly if IL-7 or IL-15 is withdrawn, human T cells can survive prolonged withdrawal of IL-7 and IL-15. Here we show that IL-7 and IL-15 are requir...

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Main Authors: Drake, Adam, Kaur, Mandeep, Iliopoulou, Bettina P., Phennicie, Ryan, Hanson, Amanda, Chen, Jianzhu, Phennicie, Ryan T.
Other Authors: Massachusetts Institute of Technology. Department of Biology
Format: Article
Language:en_US
Published: Public Library of Science 2017
Online Access:http://hdl.handle.net/1721.1/107955
https://orcid.org/0000-0001-9816-2187
https://orcid.org/0000-0002-5687-6154
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author Drake, Adam
Kaur, Mandeep
Iliopoulou, Bettina P.
Phennicie, Ryan
Hanson, Amanda
Chen, Jianzhu
Phennicie, Ryan T.
Iliopoulou, Bettina P.
author2 Massachusetts Institute of Technology. Department of Biology
author_facet Massachusetts Institute of Technology. Department of Biology
Drake, Adam
Kaur, Mandeep
Iliopoulou, Bettina P.
Phennicie, Ryan
Hanson, Amanda
Chen, Jianzhu
Phennicie, Ryan T.
Iliopoulou, Bettina P.
author_sort Drake, Adam
collection MIT
description T lymphocytes require signals from self-peptides and cytokines, most notably interleukins 7 and 15 (IL-7, IL-15), for survival. While mouse T cells die rapidly if IL-7 or IL-15 is withdrawn, human T cells can survive prolonged withdrawal of IL-7 and IL-15. Here we show that IL-7 and IL-15 are required to maintain human T cell proliferative capacity through the STAT5 signaling pathway. T cells from humanized mice proliferate better if stimulated in the presence of human IL-7 or IL-15 or if T cells are exposed to human IL-7 or IL-15 in mice. Freshly isolated T cells from human peripheral blood lose proliferative capacity if cultured for 24 hours in the absence of IL-7 or IL-15. We further show that phosphorylation of STAT5 correlates with proliferation and inhibition of STAT5 reduces proliferation. These results reveal a novel role of IL-7 and IL-15 in maintaining human T cell function, provide an explanation for T cell dysfunction in humanized mice, and have significant implications for in vitro studies with human T cells.
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spelling mit-1721.1/1079552022-09-29T17:23:46Z Interleukins 7 and 15 Maintain Human T Cell Proliferative Capacity through STAT5 Signaling Drake, Adam Kaur, Mandeep Iliopoulou, Bettina P. Phennicie, Ryan Hanson, Amanda Chen, Jianzhu Phennicie, Ryan T. Iliopoulou, Bettina P. Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Kaur, Mandeep Drake, Adam Iliopoulou, Panagiota Phennicie, Ryan T. Hanson, Amanda Chen, Jianzhu T lymphocytes require signals from self-peptides and cytokines, most notably interleukins 7 and 15 (IL-7, IL-15), for survival. While mouse T cells die rapidly if IL-7 or IL-15 is withdrawn, human T cells can survive prolonged withdrawal of IL-7 and IL-15. Here we show that IL-7 and IL-15 are required to maintain human T cell proliferative capacity through the STAT5 signaling pathway. T cells from humanized mice proliferate better if stimulated in the presence of human IL-7 or IL-15 or if T cells are exposed to human IL-7 or IL-15 in mice. Freshly isolated T cells from human peripheral blood lose proliferative capacity if cultured for 24 hours in the absence of IL-7 or IL-15. We further show that phosphorylation of STAT5 correlates with proliferation and inhibition of STAT5 reduces proliferation. These results reveal a novel role of IL-7 and IL-15 in maintaining human T cell function, provide an explanation for T cell dysfunction in humanized mice, and have significant implications for in vitro studies with human T cells. 2017-04-07T18:14:32Z 2017-04-07T18:14:32Z 2016-11 2015-09 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/107955 Drake, Adam, Mandeep Kaur, Bettina P. Iliopoulou, Ryan Phennicie, Amanda Hanson, and Jianzhu Chen. “Interleukins 7 and 15 Maintain Human T Cell Proliferative Capacity through STAT5 Signaling.” Edited by Jose C. Crispin. PLOS ONE 11, no. 11 (November 17, 2016): e0166280. https://orcid.org/0000-0001-9816-2187 https://orcid.org/0000-0002-5687-6154 en_US http://dx.doi.org/10.1371/journal.pone.0166280 PLOS ONE Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/ application/pdf Public Library of Science PLoS
spellingShingle Drake, Adam
Kaur, Mandeep
Iliopoulou, Bettina P.
Phennicie, Ryan
Hanson, Amanda
Chen, Jianzhu
Phennicie, Ryan T.
Iliopoulou, Bettina P.
Interleukins 7 and 15 Maintain Human T Cell Proliferative Capacity through STAT5 Signaling
title Interleukins 7 and 15 Maintain Human T Cell Proliferative Capacity through STAT5 Signaling
title_full Interleukins 7 and 15 Maintain Human T Cell Proliferative Capacity through STAT5 Signaling
title_fullStr Interleukins 7 and 15 Maintain Human T Cell Proliferative Capacity through STAT5 Signaling
title_full_unstemmed Interleukins 7 and 15 Maintain Human T Cell Proliferative Capacity through STAT5 Signaling
title_short Interleukins 7 and 15 Maintain Human T Cell Proliferative Capacity through STAT5 Signaling
title_sort interleukins 7 and 15 maintain human t cell proliferative capacity through stat5 signaling
url http://hdl.handle.net/1721.1/107955
https://orcid.org/0000-0001-9816-2187
https://orcid.org/0000-0002-5687-6154
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