{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T03:15:35Z","timestamp":1762917335693},"reference-count":46,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2011,8,30]],"date-time":"2011-08-30T00:00:00Z","timestamp":1314662400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2011,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Human Immune System (HIS) mice represent a novel biotechnology platform to dissect human haematopoiesis and immune responses. However, the limited human T\u2010cell development that is observed in HIS mice restricts its utility for these applications. Here, we address whether reduced thymopoiesis in HIS mice reflects an autonomous defect in T\u2010cell precursors and\/or a defect in the murine thymic niche. Human thymocyte precursors seed the mouse thymus and their reciprocal interactions with murine thymic epithelial cells (TECs) led to both T\u2010cell and TEC maturation. The human thymocyte subsets observed in HIS mice demonstrated survival, proliferative and phenotypic characteristics of their normal human counterparts, suggesting that the intrinsic developmental program of human thymocytes unfolds normally in this xenograft setting. We observed that exogenous administration of human IL\u201015\/IL\u201015R\u03b1 agonistic complexes induced the survival, proliferation and absolute numbers of immature human thymocyte subsets, without any obvious effect on cell\u2010surface phenotype or TCR V\u03b2 usage amongst the newly selected mature single\u2010positive (SP) thymocytes. Finally, when IL\u201015 was administered early after stem cell transplantation, we noted accelerated thymopoiesis resulting in the more rapid appearance of peripheral na\u00efve T cells. Our results highlight the functional capacity of murine thymic stroma cells in promoting human thymopoiesis in HIS mice but suggest that the \u201ccross\u2010talk\u201d between murine thymic stroma and human haematopoietic precursors may be suboptimal. As IL\u201015 immunotherapy promotes early thymopoiesis, this novel approach could be used to reduce the period of T\u2010cell immunodeficiency in the post\u2010transplant clinical setting.<\/jats:p>","DOI":"10.1002\/eji.201141586","type":"journal-article","created":{"date-parts":[[2011,7,8]],"date-time":"2011-07-08T18:40:06Z","timestamp":1310150406000},"page":"2883-2893","source":"Crossref","is-referenced-by-count":17,"title":["Autonomous and extrinsic regulation of thymopoiesis inhuman immune system (HIS) mice"],"prefix":"10.1002","volume":"41","author":[{"given":"Nicholas D.","family":"Huntington","sequence":"first","affiliation":[]},{"given":"Nuno L.","family":"Alves","sequence":"additional","affiliation":[]},{"given":"Nicolas","family":"Legrand","sequence":"additional","affiliation":[]},{"given":"Annick","family":"Lim","sequence":"additional","affiliation":[]},{"given":"H\u00e9l\u00e8ne","family":"Strick\u2010Marchand","sequence":"additional","affiliation":[]},{"given":"Ariane","family":"Plet","sequence":"additional","affiliation":[]},{"given":"Kees","family":"Weijer","sequence":"additional","affiliation":[]},{"given":"Yannick","family":"Jacques","sequence":"additional","affiliation":[]},{"given":"Hergen","family":"Spits","sequence":"additional","affiliation":[]},{"given":"James P.","family":"Di Santo","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2011,8,30]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-02-0656"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1093933"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20082013"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-01-0190"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0902019"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.14.1.73"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2009.07.010"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni723"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.23.021704.115715"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1781"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2006.00347.x"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.11.002"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.24.021605.090612"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/9.9.1375"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.151.5.2546"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2657"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2580"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2008.12"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.26.15068"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80664-0"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.191.5.771"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0809559106"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-03-277103"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0307442101"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0600240103"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.57.5.763"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.7.3810"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-11-3577"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2009.06.006"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20051547"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.4.2053"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-540-75647-7_7"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.2.377"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/1074-7613(95)90047-0"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.22.012703.104614"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.63.6.643"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2006.11.006"},{"key":"e_1_2_6_39_2","doi-asserted-by":"crossref","first-page":"2592","DOI":"10.4049\/jimmunol.158.6.2592","article-title":"The common gamma\u2010chain of cytokine receptors regulates intrathymic T cell development at multiple stages","volume":"158","author":"He Y. 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