{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T03:27:39Z","timestamp":1790220459445,"version":"4.1.0"},"reference-count":29,"publisher":"Rockefeller University Press","issue":"10","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2009,9,28]]},"abstract":"<jats:p>Whether thymic stromal lymphopoietin (TSLP) directly induces potent human CD4+ T cell proliferation and Th2 differentiation is unknown. We report that resting and activated CD4+ T cells expressed high levels of IL-7 receptor a chain but very low levels of TSLP receptor (TSLPR) when compared with levels expressed in myeloid dendritic cells (mDCs). This was confirmed by immunohistology and flow cytometry analyses showing that only a subset of mDCs, with more activated phenotypes, expressed TSLPR in human tonsils in vivo. IL-7 induced strong STAT1, -3, and -5 activation and promoted the proliferation of naive CD4+ T cells in the presence of anti-CD3 and anti-CD28 monoclonal antibodies, whereas TSLP induced weak STAT5 activation, associated with marginally improved cell survival and proliferation, but failed to induce cell expansion and Th2 differentiation. The effect of TSLP on enhancing strong human T cell proliferation was observed only when sorted naive CD4+ T cells were cultured with mDCs at levels as low as 0.5%. TSLP could only induce naive CD4+ T cells to differentiate into Th2 cells in the presence of allogeneic mDCs. These results demonstrate that IL-7 and TSLP use different mechanisms to regulate human CD4+ T cell homeostasis.<\/jats:p>","DOI":"10.1084\/jem.20090153","type":"journal-article","created":{"date-parts":[[2009,9,22]],"date-time":"2009-09-22T01:48:21Z","timestamp":1253584101000},"page":"2111-2119","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":81,"title":["TSLP and IL-7 use two different mechanisms to regulate human CD4+ T cell homeostasis"],"prefix":"10.1084","volume":"206","author":[{"given":"Ning","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Immunology 1 and 2"},{"name":"Center for Cancer Immunology Research, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030 1 and 2"},{"name":"Department of Immunology 1 and 2"},{"name":"Center for Cancer Immunology Research, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Hong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Immunology 1 and 2"},{"name":"Center for Cancer Immunology Research, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030 1 and 2"},{"name":"Department of Immunology 1 and 2"},{"name":"Center for Cancer Immunology Research, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yui-Hsi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Immunology 1 and 2"},{"name":"Center for Cancer Immunology Research, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030 1 and 2"},{"name":"Department of Immunology 1 and 2"},{"name":"Center for Cancer Immunology Research, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiko","family":"Arima","sequence":"additional","affiliation":[{"name":"Department of Immunology 1 and 2"},{"name":"Center for Cancer Immunology Research, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030 1 and 2"},{"name":"Department of Immunology 1 and 2"},{"name":"Center for Cancer Immunology Research, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shino","family":"Hanabuchi","sequence":"additional","affiliation":[{"name":"Department of Immunology 1 and 2"},{"name":"Center for Cancer Immunology Research, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030 1 and 2"},{"name":"Department of Immunology 1 and 2"},{"name":"Center for Cancer Immunology Research, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Jun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Immunology 1 and 2"},{"name":"Center for Cancer Immunology Research, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030 1 and 2"},{"name":"Department of Immunology 1 and 2"},{"name":"Center for Cancer Immunology Research, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2009,9,21]]},"reference":[{"key":"2023072917283919400_bib27","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1111\/j.1365-2249.2008.03731.x","article-title":"Human TSLP directly enhances expansion of CD8+ T cells","volume":"154","author":"Akamatsu","year":"2008","journal-title":"Clin. Exp. Immunol."},{"key":"2023072917283919400_bib1","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1084\/jem.20031975","article-title":"A role for thymic stromal lymphopoietin in CD4(+) T cell development","volume":"200","author":"Al-Shami","year":"2004","journal-title":"J. Exp. Med."},{"key":"2023072917283919400_bib2","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1084\/jem.20062211","article-title":"Thymic stromal lymphopoietin is released by human epithelial cells in response to microbes, trauma, or inflammation and potently activates mast cells","volume":"204","author":"Allakhverdi","year":"2007","journal-title":"J. Exp. Med."},{"key":"2023072917283919400_bib3","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1016\/j.coi.2007.04.015","article-title":"Cytokines and T-cell homeostasis","volume":"19","author":"Boyman","year":"2007","journal-title":"Curr. Opin. Immunol."},{"key":"2023072917283919400_bib4","doi-asserted-by":"publisher","first-page":"2983","DOI":"10.1073\/pnas.052714199","article-title":"Homeostatic T cell proliferation in a T cell-dendritic cell coculture system","volume":"99","author":"Ge","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072917283919400_bib28","doi-asserted-by":"publisher","first-page":"1711","DOI":"10.1084\/jem.194.12.1711","article-title":"Cytokine-driven proliferation and differentiation of human naive, central memory, and effector memory CD4(+) T cells","volume":"194","author":"Geginat","year":"2001","journal-title":"J. Exp. Med."},{"key":"2023072917283919400_bib5","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/S1074-7613(00)80093-X","article-title":"Low-affinity ligands for the TCR drive proliferation of mature CD8+ T cells in lymphopenic hosts","volume":"11","author":"Goldrath","year":"1999","journal-title":"Immunity."},{"key":"2023072917283919400_bib6","doi-asserted-by":"publisher","first-page":"11875","DOI":"10.1073\/pnas.0801532105","article-title":"TSLP acts on infiltrating effector T cells to drive allergic skin inflammation","volume":"105","author":"He","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072917283919400_bib7","doi-asserted-by":"crossref","first-page":"3288","DOI":"10.4049\/jimmunol.168.7.3288","article-title":"Uncoupling of proliferation and Stat5 activation in thymic stromal lymphopoietin-mediated signal transduction","volume":"168","author":"Isaksen","year":"2002","journal-title":"J. Immunol."},{"key":"2023072917283919400_bib8","doi-asserted-by":"publisher","first-page":"1213","DOI":"10.1084\/jem.20051135","article-title":"TSLP-activated dendritic cells induce an inflammatory T helper type 2 cell response through OX40 ligand","volume":"202","author":"Ito","year":"2005","journal-title":"J. Exp. Med."},{"key":"2023072917283919400_bib11","doi-asserted-by":"publisher","first-page":"1377","DOI":"10.1126\/science.286.5443.1377","article-title":"Persistence of memory CD8 T cells in MHC class I-deficient mice","volume":"286","author":"Murali-Krishna","year":"1999","journal-title":"Science."},{"key":"2023072917283919400_bib29","doi-asserted-by":"publisher","first-page":"1877","DOI":"10.1126\/science.8266077","article-title":"Interleukin-2 receptor gamma chain: a functional component of the interleukin-7 receptor","volume":"262","author":"Noguchi","year":"1993","journal-title":"Science."},{"key":"2023072917283919400_bib12","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.4049\/jimmunol.178.3.1396","article-title":"Induction of IL-4 expression in CD4(+) T cells by thymic stromal lymphopoietin","volume":"178","author":"Omori","year":"2007","journal-title":"J. Immunol."},{"key":"2023072917283919400_bib30","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1038\/76923","article-title":"Cloning of a receptor subunit required for signaling by thymic stromal lymphopoietin","volume":"1","author":"Pandey","year":"2000","journal-title":"Nat. Immunol."},{"key":"2023072917283919400_bib31","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1084\/jem.192.5.659","article-title":"Cloning of the murine thymic stromal lymphopoietin (TSLP) receptor: Formation of a functional heteromeric complex requires interleukin 7 receptor","volume":"192","author":"Park","year":"2000","journal-title":"J. Exp. Med."},{"key":"2023072917283919400_bib32","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1038\/3877","article-title":"Defective IL7R expression in T(-)B(+)NK(+) severe combined immunodeficiency","volume":"20","author":"Puel","year":"1998","journal-title":"Nat. Genet."},{"key":"2023072917283919400_bib14","doi-asserted-by":"crossref","first-page":"336","DOI":"10.4049\/jimmunol.167.1.336","article-title":"Human thymic stromal lymphopoietin preferentially stimulates myeloid cells","volume":"167","author":"Reche","year":"2001","journal-title":"J. Immunol."},{"key":"2023072917283919400_bib16","doi-asserted-by":"crossref","first-page":"6720","DOI":"10.4049\/jimmunol.178.11.6720","article-title":"Cutting edge: direct action of thymic stromal lymphopoietin on activated human CD4+ T cells","volume":"178","author":"Rochman","year":"2007","journal-title":"J. Immunol."},{"key":"2023072917283919400_bib33","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1126\/science.270.5237.797","article-title":"Mutation of Jak3 in a patient with SCID: essential role of Jak3 in lymphoid development","volume":"270","author":"Russell","year":"1995","journal-title":"Science."},{"key":"2023072917283919400_bib34","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1038\/80868","article-title":"Interleukin-7 mediates the homeostasis of na\u00efve and memory CD8 T cells in vivo","volume":"1","author":"Schluns","year":"2000","journal-title":"Nat. Immunol."},{"key":"2023072917283919400_bib18","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1038\/ni805","article-title":"Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP","volume":"3","author":"Soumelis","year":"2002","journal-title":"Nat. Immunol."},{"key":"2023072917283919400_bib19","doi-asserted-by":"publisher","first-page":"1701","DOI":"10.1084\/jem.20071681","article-title":"Administration of rhIL-7 in humans increases in vivo TCR repertoire diversity by preferential expansion of naive T cell subsets","volume":"205","author":"Sport\u00e8s","year":"2008","journal-title":"J. Exp. Med."},{"key":"2023072917283919400_bib20","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1111\/j.0105-2896.2006.00381.x","article-title":"CD4+ memory T cells: functional differentiation and homeostasis","volume":"211","author":"Stockinger","year":"2006","journal-title":"Immunol. Rev."},{"key":"2023072917283919400_bib21","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/S1286-4579(01)01509-X","article-title":"Regulation of na\u00efve and memory T-cell homeostasis","volume":"4","author":"Surh","year":"2002","journal-title":"Microbes Infect."},{"key":"2023072917283919400_bib22","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1111\/j.0105-2896.2006.00401.x","article-title":"Homeostasis of memory T cells","volume":"211","author":"Surh","year":"2006","journal-title":"Immunol. Rev."},{"key":"2023072917283919400_bib23","doi-asserted-by":"publisher","first-page":"8732","DOI":"10.1073\/pnas.161126098","article-title":"IL-7 is critical for homeostatic proliferation and survival of naive T cells","volume":"98","author":"Tan","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072917283919400_bib24","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1016\/j.immuni.2006.03.019","article-title":"Maintenance and polarization of human TH2 central memory T cells by thymic stromal lymphopoietin-activated dendritic cells","volume":"24","author":"Wang","year":"2006","journal-title":"Immunity."},{"key":"2023072917283919400_bib25","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1038\/ni1048","article-title":"Human thymic stromal lymphopoietin promotes dendritic cell-mediated CD4+ T cell homeostatic expansion","volume":"5","author":"Watanabe","year":"2004","journal-title":"Nat. Immunol."},{"key":"2023072917283919400_bib26","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1038\/ni1247","article-title":"Thymic stromal lymphopoietin as a key initiator of allergic airway inflammation in mice","volume":"6","author":"Zhou","year":"2005","journal-title":"Nat. Immunol."}],"container-title":["Journal of Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/206\/10\/2111\/1902510\/jem_20090153.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/206\/10\/2111\/1902510\/jem_20090153.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,29]],"date-time":"2023-07-29T17:29:02Z","timestamp":1690651742000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/206\/10\/2111\/46082\/TSLP-and-IL-7-use-two-different-mechanisms-to"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,9,21]]},"references-count":29,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2009,9,28]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.20090153","relation":{},"ISSN":["1540-9538","0022-1007"],"issn-type":[{"value":"1540-9538","type":"electronic"},{"value":"0022-1007","type":"print"}],"subject":[],"published":{"date-parts":[[2009,9,21]]}}}