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 While mouse T cells die rapidly if IL-7 or IL-15 is withdrawn, human T cells can survive prolonged withdrawal of IL-7 and IL-15.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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2017
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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 While mouse T cells die rapidly if IL-7 or IL-15 is withdrawn, human T cells can survive prolonged withdrawal of IL-7 and IL-15.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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institution | Massachusetts Institute of Technology |
language | en_US |
last_indexed | 2024-09-23T15:58:12Z |
publishDate | 2017 |
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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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