{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T07:25:22Z","timestamp":1790234722931,"version":"4.1.0"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2006,1,1]],"date-time":"2006-01-01T00:00:00Z","timestamp":1136073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Signaling lymphocyte activation molecule (SLAM) family receptors are critically involved in modulating innate and adaptive immune responses. Several SLAM family receptors have been shown to interact with the adaptor molecule SAP; however, subsequent intracellular signaling is poorly defined. Notably, mutations in SLAM-associated protein (SAP) lead to X-linked lymphoproliferative disease, a rare but fatal immunodeficiency. Although the SLAM family member Ly9 (CD229) is known to interact with SAP, the functions of this receptor have remained elusive. Therefore, we have generated Ly9\u2212\/\u2212 mice and compared their phenotype with that of SLAM\u2212\/\u2212 and SAP\u2212\/\u2212 mice. We report that Ly9\u2212\/\u2212 T cells exhibit a mild Th2 defect associated with reduced IL-4 production after stimulation with anti-TCR and anti-CD28 in vitro. This defect is similar in magnitude to the previously reported Th2 defect in SLAM\u2212\/\u2212 mice but is more subtle than that observed in SAP\u2212\/\u2212 mice. In contrast to SLAM\u2212\/\u2212 and SAP\u2212\/\u2212 mice, T cells from Ly9\u2212\/\u2212 mice proliferate poorly and produce little IL-2 after suboptimal stimulation with anti-CD3 in vitro. We have also found that Ly9\u2212\/\u2212 macrophages exhibit no defects in cytokine production or bacterial killing as was observed in SLAM\u2212\/\u2212 macrophages. Additionally, Ly9\u2212\/\u2212 mice differ from SAP\u2212\/\u2212 mice in that they foster normal development of NKT cells and mount appropriate T and B cell responses to lymphocytic choriomeningitis virus. We have identified significant phenotypic differences between Ly-9\u2212\/\u2212 mice as compared with both SLAM\u2212\/\u2212 and SAP\u2212\/\u2212 mice. Although Ly9, SLAM, and SAP play a common role in promoting Th2 polarization, Ly-9 is uniquely involved in enhancing T cell activation.<\/jats:p>","DOI":"10.4049\/jimmunol.176.1.291","type":"journal-article","created":{"date-parts":[[2014,4,23]],"date-time":"2014-04-23T09:37:11Z","timestamp":1398245831000},"page":"291-300","source":"Crossref","is-referenced-by-count":72,"title":["Ly9 (CD229)-Deficient Mice Exhibit T Cell Defects yet Do Not Share Several Phenotypic Characteristics Associated with SLAM- and SAP-Deficient Mice"],"prefix":"10.1093","volume":"176","author":[{"given":"Daniel B","family":"Graham","sequence":"first","affiliation":[{"name":"Department of Immunology , Rochester, MN 55905"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P","family":"Bell","sequence":"additional","affiliation":[{"name":"Department of Immunology , Rochester, MN 55905"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan M","family":"McCausland","sequence":"additional","affiliation":[{"name":"Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology , San Diego, CA 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine J","family":"Huntoon","sequence":"additional","affiliation":[{"name":"Department of Immunology , Rochester, MN 55905"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"van Deursen","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Adolescent Medicine , Rochester, MN 55905"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William A","family":"Faubion","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Mayo Clinic College of Medicine , Rochester, MN 55905"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shane","family":"Crotty","sequence":"additional","affiliation":[{"name":"Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology , San Diego, CA 92121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J","family":"McKean","sequence":"additional","affiliation":[{"name":"Department of Immunology , Rochester, MN 55905"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2006,1,1]]},"reference":[{"key":"2026020211363688600_R1","first-page":"7033","volume-title":"J. 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