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According to the progressive differentiation model, memory subsets generate from na\u00efve precursors in a linear and unidirectional path depending on the strength and quality of stimulatory signals. By observing human na\u00efve T cells in contact with GAD65 loaded autologous dendritic cells, we observed that approximately 10% of cells divided with the plane of cell division parallel to the one of the immune synapse, causing phenotypic asymmetries in the proximal and distal daughter T cells. After the first T cell division, proximal and distal daughter T cells showed different phenotype, metabolic signature and commitment to differentiate towards long\u2010lived memory T cells or T cells with effector function. Subjects with or without T1D showed a similar frequency of asymmetric T cell division (ATCD) for autoantigens and recall antigens specific T cells, however the frequency of ATCD is significantly increased in autoreactive T cells in patients with T1D when IL\u20107 was added to the culture. An increased upregulation of GLUT1 in response to IL\u20107 in patients with T1D was related to the rate of ATCD. Our results showed that ATCD is associated with an early divergence in the differentiation fate of na\u00efve T cells specific for GAD65 during first antigen encounter.<\/jats:p>","DOI":"10.1111\/imm.13537","type":"journal-article","created":{"date-parts":[[2022,6,26]],"date-time":"2022-06-26T08:54:05Z","timestamp":1656233645000},"page":"303-313","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Asymmetric T cell division of <scp>GAD65<\/scp> specific naive T cells contribute to an early divergence in the differentiation fate into memory T cell subsets"],"prefix":"10.1111","volume":"167","author":[{"given":"Greta","family":"Alampi","sequence":"first","affiliation":[{"name":"San Raffaele Diabetes Research Institute IRCCS Ospedale San Raffaele  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debora","family":"Vignali","sequence":"additional","affiliation":[{"name":"San Raffaele Diabetes 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