Interleukins 7 and 15 Maintain Human T Cell Proliferative Capacity through STAT5 Signaling
Author(s)
Drake, Adam; Kaur, Mandeep; Iliopoulou, Bettina P.; Phennicie, Ryan; Hanson, Amanda; Chen, Jianzhu; Phennicie, Ryan T.; Iliopoulou, Bettina P.; ... Show more Show less![Thumbnail](/bitstream/handle/1721.1/107955/Drake-2016-Interleukins%207%20and%2015%20Maintain%20Huma.pdf.jpg?sequence=4&isAllowed=y)
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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 While mouse T cells die rapidly if IL-7 or IL-15 is withdrawn, human T cells can survive prolonged withdrawal of IL-7 and IL-15.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.
Date issued
2016-11Department
Massachusetts Institute of Technology. Department of Biology; Koch Institute for Integrative Cancer Research at MITJournal
PLOS ONE
Publisher
Public Library of Science
Citation
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.
Version: Final published version
ISSN
1932-6203