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CD226\u2010deficient mice have impaired immune response capacity. The function of CD226 in regulating T cell development in the thymus, a central immune organ, is not yet fully understood. We investigated the development of thymocytes using CD226 knockout mice and single\u2010cell sequencing techniques. CD226 began to be expressed in the second half of thymocyte development, with a gradual increase from the double\u2010positive (DP) to single\u2010positive (SP) phase and higher levels of CD226 on CD8+ T cells than on CD4+ T cells from the SP phase to mature T cells. In the thymus of CD226KO mice, the proportion of DPT at the quiescent phase (DPT\u2010Q) increased, of which the Gzma+ cluster that tends to be CD8+ T cells and CD5+ cluster that is undergoing positive selection decreased dramatically. Afterward, the proportion of mature CD8+ T cells reduced dramatically. Depletion of CD226 impaired TCR activation signalling and diminished AKT\/ERK\/NF\u2010\u03baB\/p38 phosphorylation levels. The diminished TCR responsiveness of DPT cells impeded their positive selection process and influenced the maturation of CD8+ T cells. In mechanism, CD226 knockout enhanced DPT cell apoptosis via impairing AKT phosphorylation. These results suggest that CD226 plays a significant role in T cell thymic development via modulation of TCR signalling, affecting CD8+ T cell maturation.<\/jats:p>","DOI":"10.1111\/imm.13612","type":"journal-article","created":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T13:34:44Z","timestamp":1669296884000},"page":"83-95","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["<scp>CD226<\/scp> knockout reduces the development of <scp>CD8<\/scp>+ T by impairing the <scp>TCR<\/scp> sensitivity of double\u2010positive thymocytes"],"prefix":"10.1111","volume":"169","author":[{"given":"Jingchang","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Immunology Fourth Military Medical University  Xi'an Shaanxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yitian","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Immunology Fourth Military Medical 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