{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:45:01Z","timestamp":1791301501175,"version":"4.1.0"},"reference-count":30,"publisher":"Rockefeller University Press","issue":"5","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2000,3,6]]},"abstract":"<jats:p>PD-1 is an immunoglobulin superfamily member bearing an immunoreceptor tyrosine-based inhibitory motif, and disruption of the PD-1 gene results in the development of lupus-like autoimmune diseases. In this study, we examined effects of the PD-1 deficiency on the thymocyte differentiation at the clonal level using T cell receptor (TCR)-\u03b2 (V\u03b28) and TCR-\u03b1\/\u03b2 (H-Y and 2C) transgenic mice. In these TCR transgenic lines, PD-1 expression in the thymus was variably augmented, but as in the normal mice, confined largely to the CD4\u2212CD8\u2212 thymocytes. The transgenic mice crossed with PD-1\u2212\/\u2212 mice in the neutral genetic backgrounds exhibited selective increase in the CD4+CD8+ (DP) population with little effect on other thymocytes subsets. Similarly, the absence of PD-1 facilitated expansion of DP thymocytes in recombination activating gene (RAG)-2\u2212\/\u2212 mice by anti-CD3\u03b5 antibody injection. On the other hand, H-Y or 2C transgenic PD-1\u2212\/\u2212 mice with the positively selecting background showed significantly reduced efficiency for the generation of CD8+ single positive cells bearing the transgenic TCR-\u03b1\/\u03b2 in spite of the increased DP population. These results collectively indicate that PD-1 negatively regulates the \u03b2 selection and modulates the positive selection, and suggest that PD-1 deficiency may lead to the significant alteration of mature T cell repertoire.<\/jats:p>","DOI":"10.1084\/jem.191.5.891","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T12:48:33Z","timestamp":1027687713000},"page":"891-898","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":170,"title":["Facilitation of \u03b2 Selection and Modification of Positive Selection in the Thymus of Pd-1\u2013Deficient Mice"],"prefix":"10.1084","volume":"191","author":[{"given":"Hiroyuki","family":"Nishimura","sequence":"first","affiliation":[{"name":"aDepartment of Medical Chemistry, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tasuku","family":"Honjo","sequence":"additional","affiliation":[{"name":"aDepartment of Medical Chemistry, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nagahiro","family":"Minato","sequence":"additional","affiliation":[{"name":"bDepartment of Immunology and Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2000,3,6]]},"reference":[{"key":"2023072509093888100_R1","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/S0065-2776(08)60620-3","article-title":"Development and selection of T cellsfacts and puzzles","volume":"58","author":"Kisielow","year":"1995","journal-title":"Adv. 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Natl. Acad. Sci. USA."},{"key":"2023072509093888100_R23","doi-asserted-by":"crossref","first-page":"9729","DOI":"10.1073\/pnas.85.24.9729","article-title":"Early expression of a T-cell receptor beta-chain transgene suppresses rearrangement of the V gamma 4 gene segment","volume":"85","author":"von Boehmer","year":"1988","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072509093888100_R24","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1002\/j.1460-2075.1991.tb07924.x","article-title":"Surface expression of the beta T cell receptor (TCR) chain in the absence of other TCR or CD3 proteins on immature T cells","volume":"10","author":"Kishi","year":"1991","journal-title":"EMBO (Eur. Mol. Biol. Organ.) J."},{"key":"2023072509093888100_R25","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1084\/jem.186.5.767","article-title":"Allelic exclusion in pT\u03b1-deficient miceno evidence for cell surface expression of two T cell receptor (TCR)-\u03b2 chains, but less efficient inhibition of endogenous V\u03b2\u2192(D)J\u03b2 rearrangements in the presence of a functional TCR-\u03b2 transgene","volume":"186","author":"Krotkova","year":"1997","journal-title":"J. Exp. Med."},{"key":"2023072509093888100_R26","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1084\/jem.185.9.1541","article-title":"Role of different T cell receptors in the development of pre-T cells","volume":"185","author":"Buer","year":"1997","journal-title":"J. Exp. 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