{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T04:43:05Z","timestamp":1745815385495,"version":"3.40.3"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2011,4,1]],"date-time":"2011-04-01T00:00:00Z","timestamp":1301616000000},"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":[[2011,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The Gads adaptor protein is critical for TCR-mediated Ca2+ mobilization. We investigated the effect of Gads deficiency on the proliferation of CD8+ T cells following peptide stimulation and in the context of infection with an intracellular pathogen. We stimulated CD8+ T cells from Gads+\/+ OT-I and Gads\u2212\/\u2212 OT-I mice with cognate Ag (SIINFEKL) or altered peptide ligand. In vitro experiments revealed that Gads was required for optimal proliferation of CD8+ T cells. This defect was most evident at the early time points of proliferation and when low doses of Ag were used as stimuli. Cell cycle analysis demonstrated that Gads\u2212\/\u2212 CD8+ T cells had impaired TCR-mediated exit from the G0 phase of the cell cycle. Furthermore, Gads\u2212\/\u2212 CD8+ T cells had delayed expression of c-myc and CD69 upon the stimulation with SIINFEKL. We then investigated how Gads deficiency would impact CD8+ T cell-mediated immunity in the context of infection with an intracellular pathogen. At early time points, Gads+\/+ and Gads\u2212\/\u2212 CD8+ T cells proliferated to a similar extent, despite the fact that expression of CD69 and CD25 was reduced in the absence of Gads. After 5 d postinfection, Gads was required to sustain the expansion phase of the immune response; the peak response of Gads\u2212\/\u2212 cells was significantly lower than for Gads+\/+ cells. However, Gads was not required for the differentiation of naive CD8+ T cells into memory cells. We conclude that the primary function of Gads is to regulate the sensitivity of the TCR to Ag ligation.<\/jats:p>","DOI":"10.4049\/jimmunol.1001604","type":"journal-article","created":{"date-parts":[[2011,3,17]],"date-time":"2011-03-17T01:32:41Z","timestamp":1300325561000},"page":"4579-4589","source":"Crossref","is-referenced-by-count":5,"title":["Gads Regulates the Expansion Phase of CD8+ T Cell-Mediated Immunity"],"prefix":"10.1093","volume":"186","author":[{"given":"Elizabeth Yan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Microbiology, Molecular Genetics, and Immunology, University of Kansas Medical Center , Kansas City, KS 66160"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brooks L","family":"Parker","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Molecular Genetics, and Immunology, University of Kansas Medical Center , Kansas City, KS 66160"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas M","family":"Yankee","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Molecular Genetics, and Immunology, University of Kansas Medical Center , Kansas City, KS 66160"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2011,4,15]]},"reference":[{"key":"2025032411194465200_r1","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/S1074-7613(00)80605-6","article-title":"Helper T cell differentiation is controlled by the cell cycle","volume":"9","author":"Bird","year":"1998","journal-title":"Immunity"},{"key":"2025032411194465200_r2","doi-asserted-by":"crossref","first-page":"5338","DOI":"10.4049\/jimmunol.161.10.5338","article-title":"Differentiation of naive CTL to effector and memory CTL: correlation of effector function with phenotype and cell division","volume":"161","author":"Oehen","year":"1998","journal-title":"J. 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