{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T11:42:47Z","timestamp":1778067767736,"version":"3.51.4"},"reference-count":37,"publisher":"Rockefeller University Press","issue":"12","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2005,6,20]]},"abstract":"<jats:p>The significance of cytokine production by CD4+ regulatory T (T reg) cells after antigen exposure in vivo and its impact on their regulatory activity remains unclear. Pretreatment with donor alloantigen under the cover of anti-CD4 therapy generates alloantigen reactive T reg cells that can prevent rejection of donor-specific skin grafts that are mediated by naive CD45RBhighCD4+ T cells. To examine the kinetics and importance of cytokine gene transcription by such alloantigen-reactive T reg cells, pretreated mice were rechallenged with donor alloantigen in vivo. CD25+CD4+ T cells, but not CD25\u2212CD4+ T cells, showed a fivefold increase in IFN-\u03b3 mRNA expression within 24 h of reencountering alloantigen in vivo. This expression kinetic was highly antigen-specific and was of functional significance. Neutralizing IFN-\u03b3 at the time of cotransfer of alloantigen reactive T reg cells, together with CD45RBhighCD4+ effector T cells into Rag\u2212\/\u2212 skin graft recipients, resulted in skin graft necrosis in all recipients; the generation and function of alloantigen-reactive T reg cells was impaired dramatically in IFN-\u03b3\u2013deficient mice. These data support a unique role for IFN-\u03b3 in the functional activity of alloantigen-reactive T reg cells during the development of operational tolerance to donor alloantigens in vivo.<\/jats:p>","DOI":"10.1084\/jem.20050419","type":"journal-article","created":{"date-parts":[[2005,6,20]],"date-time":"2005-06-20T20:13:12Z","timestamp":1119298392000},"page":"1925-1935","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":239,"title":["IFN-\u03b3 production by alloantigen-reactive regulatory T cells is important for their regulatory function in vivo"],"prefix":"10.1084","volume":"201","author":[{"given":"Birgit","family":"Sawitzki","sequence":"first","affiliation":[{"name":"1Nuffield Department of Surgery, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, England, UK"},{"name":"2Institute of Medical Immunology, Charite\u0301, 10117 Berlin, Germany"}]},{"given":"Cherry I.","family":"Kingsley","sequence":"additional","affiliation":[{"name":"1Nuffield Department of Surgery, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, England, UK"}]},{"given":"Vanessa","family":"Oliveira","sequence":"additional","affiliation":[{"name":"1Nuffield Department of Surgery, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, England, UK"}]},{"given":"Mahzuz","family":"Karim","sequence":"additional","affiliation":[{"name":"1Nuffield Department of Surgery, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, England, UK"}]},{"given":"Manuela","family":"Herber","sequence":"additional","affiliation":[{"name":"1Nuffield Department of Surgery, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, England, UK"}]},{"given":"Kathryn J.","family":"Wood","sequence":"additional","affiliation":[{"name":"1Nuffield Department of Surgery, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, England, UK"}]}],"member":"291","published-online":{"date-parts":[[2005,6,20]]},"reference":[{"key":"2023072512480862500_BIB1","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1084\/jem.190.7.995","volume":"190","year":"1999","journal-title":"J. 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