title: Interleukins 7 and 15 Maintain Human T Cell Proliferative Capacity through STAT5 Signaling.
abstract: 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 While mouse T cells die rapidly if IL-7 or IL-15 is withdrawn, human T cells can survive prolonged withdrawal of IL-7 and IL-15.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.
authors.affiliation: Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States of America.
authors.forename: Adam
authors.initials: A
authors.lastname: Drake
authors.affiliation: Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States of America.
authors.forename: Mandeep
authors.initials: M
authors.lastname: Kaur
authors.affiliation: Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States of America.
authors.forename: Bettina P
authors.initials: BP
authors.lastname: Iliopoulou
authors.affiliation: Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States of America.
authors.forename: Ryan
authors.initials: R
authors.lastname: Phennicie
authors.affiliation: Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States of America.
authors.forename: Amanda
authors.initials: A
authors.lastname: Hanson
authors.affiliation: Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States of America.
authors.forename: Jianzhu
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D006801:Humans; D019409:Interleukin-15 / Q000378:metabolism*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D015851:Interleukin-7 / Q000378:metabolism*; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D051379:Mice; D010766:Phosphorylation; D050799:STAT5 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D019409:Interleukin-15; D053645:Interleukin-2 Receptor alpha Subunit; D015851:Interleukin-7; D050799:STAT5 Transcription Factor