{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:02:23Z","timestamp":1790766143459,"version":"4.1.0"},"reference-count":71,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2011,1,1]],"date-time":"2011-01-01T00:00:00Z","timestamp":1293840000000},"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":[[2011,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The first TCR-dependent checkpoint in the thymus determines \u03b1\u03b2 versus \u03b3\u03b4 T lineage fate and sets the stage for later T cell differentiation decisions. We had previously shown that early T cells in NOD mice that are unable to rearrange a TCR exhibit a defect in checkpoint enforcement at this stage. To determine if T cell progenitors from wild-type NOD mice also exhibit cell-autonomous defects in development, we investigated their differentiation in the Notch-ligand\u2013presenting OP9-DL1 coculture system, as well as by analysis of T cell development in vivo. Cultured CD4 and CD8 double-negative cells from NOD mice exhibited major defects in the generation of CD4 and CD8 double-positive \u03b1\u03b2 T cells, whereas \u03b3\u03b4 T cell development from bipotent precursors was enhanced. Limiting dilution and single-cell experiments show that the divergent effects on \u03b1\u03b2 and \u03b3\u03b4 T cell development did not spring from biased lineage choice but from increased proliferation of \u03b3\u03b4 T cells and impaired accumulation of \u03b1\u03b2 T lineage double-positive cells. In vivo, NOD early T cell subsets in the thymus also show characteristics indicative of defective \u03b2-selection, and peripheral \u03b1\u03b2 T cells are poorly established in mixed bone marrow chimeras, contrasting with strong \u03b3\u03b4 T as well as B cell repopulation. Thus, NOD T cell precursors reveal divergent, lineage-specific differentiation abnormalities in vitro and in vivo from the first TCR-dependent developmental choice point, which may have consequences for subsequent lineage decisions and effector functions.<\/jats:p>","DOI":"10.4049\/jimmunol.1002630","type":"journal-article","created":{"date-parts":[[2010,12,10]],"date-time":"2010-12-10T22:58:45Z","timestamp":1292021925000},"page":"826-837","source":"Crossref","is-referenced-by-count":12,"title":["Lineage Divergence at the First TCR-Dependent Checkpoint: Preferential \u03b3\u03b4 and Impaired \u03b1\u03b2 T Cell Development in Nonobese Diabetic Mice"],"prefix":"10.1093","volume":"186","author":[{"given":"Ni","family":"Feng","sequence":"first","affiliation":[{"name":"Division of Biology, California Institute of Technology , Pasadena, CA 91125"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Vegh","sequence":"additional","affiliation":[{"name":"Division of Biology, California Institute of Technology , Pasadena, CA 91125"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen V","family":"Rothenberg","sequence":"additional","affiliation":[{"name":"Division of Biology, California Institute of Technology , Pasadena, CA 91125"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary A","family":"Yui","sequence":"additional","affiliation":[{"name":"Division of Biology, California Institute of Technology , Pasadena, CA 91125"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,1,15]]},"reference":[{"key":"2025032410575466400_r1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/nri2232","article-title":"Launching the T-cell-lineage developmental programme","volume":"8","author":"Rothenberg","year":"2008","journal-title":"Nat. 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