{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:12:42Z","timestamp":1791295962105,"version":"4.1.0"},"reference-count":24,"publisher":"Rockefeller University Press","issue":"9","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2004,11,1]]},"abstract":"<jats:p>Interleukin (IL)-7 receptor (R) signaling is essential for T and B lymphopoiesis by promoting proliferation, differentiation, and survival of cells. Mice lacking either IL-7 or the IL-7R\u03b1 chain have abnormally low numbers of immature as well as mature T and B lymphocytes. Transgenic expression of the apoptosis inhibitor Bcl-2 rescues T cell development and function in IL-7R\u03b1\u2013deficient mice, indicating that activation of a proapoptotic Bcl-2 family member causes death of immature and mature T cells. BH3-only proteins such as Bim, which are distant proapoptotic members of the Bcl-2 family, are essential initiators of programmed cell death and stress-induced apoptosis. We generated Bim\/IL-7R\u03b1 double deficient mice and found that loss of Bim significantly increased thymocyte numbers, restored near normal numbers of mature T cells in the blood and spleen, and enhanced cytotoxic T cell responses to virus infection in IL-7R\u03b1\u2212\/\u2212 mice. These results indicate that Bim cooperates with other proapoptotic proteins in the death of IL-7\u2013deprived T cell progenitors in vivo, but is the major inducer of this pathway to apoptosis in mature T cells. This indicates that pharmacological inhibition of Bim function might be useful for boosting immune responses in immunodeficient patients.<\/jats:p>","DOI":"10.1084\/jem.20041328","type":"journal-article","created":{"date-parts":[[2004,10,26]],"date-time":"2004-10-26T00:14:00Z","timestamp":1098749640000},"page":"1189-1195","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":108,"title":["Loss of Bim Increases T Cell Production and Function in Interleukin 7 Receptor\u2013deficient Mice"],"prefix":"10.1084","volume":"200","author":[{"given":"Marc","family":"Pellegrini","sequence":"first","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Bouillet","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikara","family":"Robati","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabrielle T.","family":"Belz","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gayle M.","family":"Davey","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Strasser","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2004,10,25]]},"reference":[{"key":"2023072512433923900_BIB1","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.1126\/science.8266077","volume":"262","year":"1993","journal-title":"Science."},{"key":"2023072512433923900_BIB2","doi-asserted-by":"crossref","first-page":"561","DOI":"10.4049\/jimmunol.147.2.561","volume":"147","year":"1991","journal-title":"J. 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