{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T14:44:09Z","timestamp":1790520249151,"version":"4.1.0"},"reference-count":35,"publisher":"National Academy of Sciences","issue":"27","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2007,7,3]]},"abstract":"<jats:p>\n                    The 5\u2032-phosphoinositol phosphatase SHIP negatively regulates signaling pathways triggered by antigen, cytokine and Fc receptors in both lymphocytes and myeloid cells. Mice with germ-line (null) deletion of SHIP develop a myeloproliferative-like syndrome that causes early lethality. Lymphocyte anomalies have been observed in SHIP-null mice, but it is unclear whether they are due to an intrinsic requirement of SHIP in these cells or a consequence of the severe myeloid pathology. To precisely address the function of SHIP in T cells, we have generated mice with T cell-specific deletion of SHIP. In the absence of SHIP, we found no differences in thymic selection or in the activation state and numbers of regulatory T cells in the periphery. In contrast, SHIP-deficient T cells do not skew efficiently to Th2\n                    <jats:italic>in vitro<\/jats:italic>\n                    . Mice with T cell-specific deletion of SHIP show poor antibody responses on Alum\/NP-CGG immunization and diminished Th2 cytokine production when challenged with\n                    <jats:italic>Schistosoma mansoni<\/jats:italic>\n                    eggs. The failure to skew to Th2 responses may be the consequence of increased basal levels of the Th1-associated transcriptional factor T-bet, resulting from enhanced sensitivity to cytokine-mediated T-bet induction. SHIP-deficient CD8\n                    <jats:sup>+<\/jats:sup>\n                    cells show enhanced cytotoxic responses, consistent with elevated T-bet levels in these cells. Overall our experiments indicate that in T cells SHIP negatively regulates cytokine-mediated activation in a way that allows effective Th2 responses and limits T cell cytotoxicity.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0704853104","type":"journal-article","created":{"date-parts":[[2007,6,21]],"date-time":"2007-06-21T21:24:08Z","timestamp":1182461048000},"page":"11382-11387","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":81,"title":["T cell-specific deletion of the inositol phosphatase SHIP reveals its role in regulating Th1\/Th2 and cytotoxic responses"],"prefix":"10.1073","volume":"104","author":[{"given":"Tatyana","family":"Tarasenko","sequence":"first","affiliation":[{"name":"Laboratories of *Immunogenetics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hemanta K.","family":"Kole","sequence":"additional","affiliation":[{"name":"Laboratories of *Immunogenetics 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