{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T07:12:34Z","timestamp":1777101154209,"version":"3.51.4"},"reference-count":43,"publisher":"Rockefeller University Press","issue":"10","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2007,10,1]]},"abstract":"<jats:p>The host responds to lymphopenic environments by acute homeostatic proliferation, which is a cytokine- and endogenous peptide-driven expansion of lymphocytes that restores the numbers and diversity of T cells. It is unknown how these homeostatically proliferating (HP) cells are ultimately controlled. Using a system where lymphocytic choriomeningitis virus\u2013immune C57BL\/6 splenocytes were transferred into lymphopenic T cell\u2013deficient hosts and allowed to reconstitute the environment, we defined the following three populations of T cells: slowly dividing Ly6C+ cells, which contained bona fide virus-specific memory cells, and more rapidly dividing Ly6C\u2212 cells segregating into programmed death (PD)-1+ and PD-1\u2212 fractions. The PD-1+ HP cell population, which peaked in frequency at day 21, was dysfunctional in that it failed to produce interferon \u03b3 or tumor necrosis factor \u03b1 on T cell receptor (TCR) stimulation, had down-regulated expression of interleukin (IL)-7R\u03b1, IL-15R\u03b2, and Bcl-2, and reacted with Annexin V, which is indicative of a preapoptotic state. The PD-1+ HP cells, in contrast to other HP cell fractions, displayed highly skewed TCR repertoires, which is indicative of oligoclonal expansion; these skewed repertoires and the PD-1+ population disappeared by day 70 from the host, presumably because of apoptosis. These results suggest that PD-1 may play a negative regulatory role to control rapidly proliferating and potentially pathogenic autoreactive CD8+ T cells during homeostatic reconstitution of lymphopenic environments.<\/jats:p>","DOI":"10.1084\/jem.20062150","type":"journal-article","created":{"date-parts":[[2007,9,5]],"date-time":"2007-09-05T00:54:25Z","timestamp":1188953665000},"page":"2321-2333","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":55,"title":["Programmed death-1 (PD-1) defines a transient and dysfunctional oligoclonal T cell population in acute homeostatic proliferation"],"prefix":"10.1084","volume":"204","author":[{"given":"Sue-Jane","family":"Lin","sequence":"first","affiliation":[{"name":"1Department of Pathology"},{"name":"2Program in Immunology and Virology, University of Massachusetts Medical School, Worcester, MA 01655"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Craig D.","family":"Peacock","sequence":"additional","affiliation":[{"name":"1Department of Pathology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kapil","family":"Bahl","sequence":"additional","affiliation":[{"name":"1Department of Pathology"},{"name":"2Program in Immunology and Virology, University of Massachusetts Medical School, Worcester, MA 01655"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raymond M.","family":"Welsh","sequence":"additional","affiliation":[{"name":"1Department of Pathology"},{"name":"2Program in Immunology and Virology, University of Massachusetts Medical School, Worcester, MA 01655"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"291","published-online":{"date-parts":[[2007,9,4]]},"reference":[{"key":"2023072515150695000_BIB1","doi-asserted-by":"crossref","first-page":"655","DOI":"10.4049\/jimmunol.171.2.655","volume":"171","year":"2003","journal-title":"J. Immunol."},{"key":"2023072515150695000_BIB2","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/S1074-7613(00)80092-8","volume":"11","year":"1999","journal-title":"Immunity."},{"key":"2023072515150695000_BIB3","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1073\/pnas.98.4.1728","volume":"98","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072515150695000_BIB4","doi-asserted-by":"crossref","first-page":"3158","DOI":"10.4049\/jimmunol.174.6.3158","volume":"174","year":"2005","journal-title":"J. Immunol."},{"key":"2023072515150695000_BIB5","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1084\/jem.192.4.557","volume":"192","year":"2000","journal-title":"J. Exp. Med."},{"key":"2023072515150695000_BIB6","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1084\/jem.192.4.549","volume":"192","year":"2000","journal-title":"J. Exp. Med."},{"key":"2023072515150695000_BIB7","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.4049\/jimmunol.165.4.1733","volume":"165","year":"2000","journal-title":"J. Immunol."},{"key":"2023072515150695000_BIB8","doi-asserted-by":"crossref","first-page":"40","DOI":"10.4049\/jimmunol.172.1.40","volume":"172","year":"2004","journal-title":"J. Immunol."},{"key":"2023072515150695000_BIB9","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0092-8674(04)00335-6","volume":"117","year":"2004","journal-title":"Cell."},{"key":"2023072515150695000_BIB10","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/S1471-4906(00)01841-X","volume":"22","year":"2001","journal-title":"Trends Immunol."},{"key":"2023072515150695000_BIB11","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.imlet.2004.10.022","volume":"98","year":"2005","journal-title":"Immunol. Lett."},{"key":"2023072515150695000_BIB12","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.it.2004.11.006","volume":"26","year":"2005","journal-title":"Trends Immunol."},{"key":"2023072515150695000_BIB13","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1186\/ar1208","volume":"6","year":"2004","journal-title":"Arthritis Res. Ther."},{"key":"2023072515150695000_BIB14","doi-asserted-by":"crossref","first-page":"3887","DOI":"10.1002\/j.1460-2075.1992.tb05481.x","volume":"11","year":"1992","journal-title":"EMBO J."},{"key":"2023072515150695000_BIB15","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1146\/annurev.immunol.23.021704.115611","volume":"23","year":"2005","journal-title":"Annu. Rev. Immunol."},{"key":"2023072515150695000_BIB16","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.cell.2006.01.022","volume":"124","year":"2006","journal-title":"Cell."},{"key":"2023072515150695000_BIB17","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.it.2006.02.001","volume":"27","year":"2006","journal-title":"Trends Immunol."},{"key":"2023072515150695000_BIB18","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/ni0306-227","volume":"7","year":"2006","journal-title":"Nat. Immunol."},{"key":"2023072515150695000_BIB19","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/S1074-7613(00)80089-8","volume":"11","year":"1999","journal-title":"Immunity."},{"key":"2023072515150695000_BIB20","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1126\/science.291.5502.319","volume":"291","year":"2001","journal-title":"Science."},{"key":"2023072515150695000_BIB21","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1038\/nm955","volume":"9","year":"2003","journal-title":"Nat. Med."},{"key":"2023072515150695000_BIB22","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1002\/art.21058","volume":"52","year":"2005","journal-title":"Arthritis Rheum."},{"key":"2023072515150695000_BIB23","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1046\/j.1399-0039.2003.00136.x","volume":"62","year":"2003","journal-title":"Tissue Antigens."},{"key":"2023072515150695000_BIB24","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1002\/art.20040","volume":"50","year":"2004","journal-title":"Arthritis Rheum."},{"key":"2023072515150695000_BIB25","doi-asserted-by":"crossref","first-page":"5535","DOI":"10.1128\/JVI.78.11.5535-5545.2004","volume":"78","year":"2004","journal-title":"J. Virol."},{"key":"2023072515150695000_BIB26","doi-asserted-by":"crossref","first-page":"F9","DOI":"10.1084\/jem.192.4.F9","volume":"192","year":"2000","journal-title":"J. Exp. Med."},{"key":"2023072515150695000_BIB27","doi-asserted-by":"crossref","first-page":"162","DOI":"10.4049\/jimmunol.175.1.162","volume":"175","year":"2005","journal-title":"J. Immunol."},{"key":"2023072515150695000_BIB28","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1084\/jem.20020033","volume":"195","year":"2002","journal-title":"J. Exp. Med."},{"key":"2023072515150695000_BIB29","doi-asserted-by":"crossref","first-page":"5138","DOI":"10.4049\/jimmunol.173.8.5138","volume":"173","year":"2004","journal-title":"J. Immunol."},{"key":"2023072515150695000_BIB30","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1038\/ni1009","volume":"4","year":"2003","journal-title":"Nat. Immunol."},{"key":"2023072515150695000_BIB31","doi-asserted-by":"crossref","first-page":"3950","DOI":"10.4049\/jimmunol.164.8.3950","volume":"164","year":"2000","journal-title":"J. Immunol."},{"key":"2023072515150695000_BIB32","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1038\/nature04444","volume":"439","year":"2006","journal-title":"Nature."},{"key":"2023072515150695000_BIB33","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1038\/nature05115","volume":"443","year":"2006","journal-title":"Nature."},{"key":"2023072515150695000_BIB34","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1038\/nm1482","volume":"12","year":"2006","journal-title":"Nat. Med."},{"key":"2023072515150695000_BIB35","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.4049\/jimmunol.171.3.1272","volume":"171","year":"2003","journal-title":"J. Immunol."},{"key":"2023072515150695000_BIB36","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1093\/intimm\/8.5.765","volume":"8","year":"1996","journal-title":"Int. Immunol."},{"key":"2023072515150695000_BIB37","doi-asserted-by":"crossref","first-page":"5538","DOI":"10.4049\/jimmunol.169.10.5538","volume":"169","year":"2002","journal-title":"J. Immunol."},{"key":"2023072515150695000_BIB38","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/S1074-7613(03)00116-X","volume":"18","year":"2003","journal-title":"Immunity."},{"key":"2023072515150695000_BIB39","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1084\/jem.183.4.1367","volume":"183","year":"1996","journal-title":"J. Exp. Med."},{"key":"2023072515150695000_BIB40","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/365053a0","volume":"365","year":"1993","journal-title":"Nature."},{"key":"2023072515150695000_BIB41","doi-asserted-by":"crossref","first-page":"3065","DOI":"10.1073\/pnas.95.6.3065","volume":"95","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072515150695000_BIB42","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1126\/science.1900951","volume":"251","year":"1991","journal-title":"Science."},{"key":"2023072515150695000_BIB43","doi-asserted-by":"crossref","first-page":"2399","DOI":"10.4049\/jimmunol.151.5.2399","volume":"151","year":"1993","journal-title":"J. Immunol."}],"container-title":["The Journal of Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/204\/10\/2321\/1722888\/jem_20062150.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/204\/10\/2321\/1722888\/jem_20062150.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T16:35:41Z","timestamp":1690302941000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/204\/10\/2321\/46663\/Programmed-death-1-PD-1-defines-a-transient-and"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,9,4]]},"references-count":43,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2007,10,1]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.20062150","relation":{},"ISSN":["1540-9538","0022-1007"],"issn-type":[{"value":"1540-9538","type":"electronic"},{"value":"0022-1007","type":"print"}],"subject":[],"published":{"date-parts":[[2007,9,4]]}}}