{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T05:42:09Z","timestamp":1793425329662,"version":"4.5.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2006,2,1]],"date-time":"2006-02-01T00:00:00Z","timestamp":1138752000000},"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":[[2006,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Itk and Rlk are members of the Tec kinase family of nonreceptor protein tyrosine kinases that are expressed in T cells, NK cells, and mast cells. These proteins are involved in the regulation of signaling processes downstream of the TCR in CD4+ T cells, particularly in the phosphorylation of phospholipase C-\u03b31 after TCR activation; furthermore, both Itk and Rlk are important in CD4+ T cell development, differentiation, function, and homeostasis. However, few studies have addressed the roles of these kinases in CD8+ T cell signaling and function. Using Itk\u2212\/\u2212 and Itk\u2212\/\u2212Rlk\u2212\/\u2212 mice, we examined the roles of these Tec family kinases in CD8+ T cells, both in vitro and in vivo. These studies demonstrate that the loss of Itk and Rlk impairs TCR-dependent signaling, causing defects in phospholipase C-\u03b31, p38, and ERK activation as well as defects in calcium flux and cytokine production in vitro and expansion and effector cytokine production by CD8+ T cells in response to viral infection. These defects cannot be rescued by providing virus-specific CD4+ T cell help, thereby substantiating the important role of Tec kinases in CD8+ T cell signaling.<\/jats:p>","DOI":"10.4049\/jimmunol.176.3.1571","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T18:20:05Z","timestamp":1398018005000},"page":"1571-1581","source":"Crossref","is-referenced-by-count":48,"title":["Tec Kinases Itk and Rlk Are Required for CD8+ T Cell Responses to Virus Infection Independent of Their Role in CD4+ T Cell Help"],"prefix":"10.1093","volume":"176","author":[{"given":"Luana O","family":"Atherly","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Massachusetts Medical School , Worcester, MA 01655"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A","family":"Brehm","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Massachusetts Medical School , Worcester, MA 01655"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond M","family":"Welsh","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Massachusetts Medical School , Worcester, MA 01655"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie J","family":"Berg","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Massachusetts Medical School , Worcester, MA 01655"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2006,2,1]]},"reference":[{"key":"2026020214085780600_R1","first-page":"199","volume-title":"Mol. 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