{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T01:26:47Z","timestamp":1791163607458,"version":"4.1.0"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2009,1,1]],"date-time":"2009-01-01T00:00:00Z","timestamp":1230768000000},"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":[[2009,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The cytokine B cell activation factor of the TNF family (BAFF) is considered to perform a proinflammatory function. This paradigm is particularly true for B cell-dependent immune responses; however the exact role for BAFF in regulating T cell immunity is ill-defined. To directly assess the effect of BAFF upon T cells, we analyzed T cell-dependent immune responses in BAFF-transgenic (Tg) mice. We found that T cell responses in BAFF-Tg mice are profoundly compromised, as indicated by their acceptance of islet allografts and delayed skin graft rejection. However, purified BAFF-Tg effector T cells could reject islet allografts with a normal kinetic, suggesting that the altered response did not relate to a defect in T cell function per se. Rather, we found that BAFF-Tg mice harbored an increased number of peripheral CD4+Foxp3+ T cells. A large proportion of the BAFF-expanded CD4+CD25+Foxp3+ regulatory T cells (Tregs) were CD62LlowCD103high and ICAM-1high, a phenotype consistent with an ability to home to inflammatory sites and prevent T cell effector responses. Indeed, depletion of the endogenous BAFF-Tg Tregs allowed allograft rejection to proceed, demonstrating that the increased Tregs were responsible for preventing alloimmunity. The ability of BAFF to promote Treg expansion was not T cell intrinsic, as Tregs did not express high levels of BAFF receptor 3, nor did excessive BAFF trigger NF-\u03baB2 processing in Tregs. In contrast, we found that BAFF engendered Treg expansion through an indirect, B cell-dependent mechanism. Thus, under certain conditions, BAFF can play a surprising anti-inflammatory role in T cell biology by promoting the expansion of Treg cells.<\/jats:p>","DOI":"10.4049\/jimmunol.182.2.793","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:00:37Z","timestamp":1397847637000},"page":"793-801","source":"Crossref","is-referenced-by-count":95,"title":["Increased CD4+Foxp3+ T Cells in BAFF-Transgenic Mice Suppress T Cell Effector Responses"],"prefix":"10.1093","volume":"182","author":[{"given":"Stacey","family":"Walters","sequence":"first","affiliation":[{"name":"Immunology and inflammation Program, Garvan Institute of Medical Research , Darlinghurst, New South Wales,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kylie E","family":"Webster","sequence":"additional","affiliation":[{"name":"Immunology and inflammation Program, Garvan Institute of Medical Research , Darlinghurst, New South Wales,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Sutherland","sequence":"additional","affiliation":[{"name":"Immunology and inflammation Program, Garvan Institute of Medical Research , Darlinghurst, New South Wales,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Gardam","sequence":"additional","affiliation":[{"name":"Immunology and inflammation Program, Garvan Institute of Medical Research , Darlinghurst, New South Wales,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Groom","sequence":"additional","affiliation":[{"name":"Immunology and inflammation Program, Garvan Institute of Medical Research , Darlinghurst, New South Wales,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Liuwantara","sequence":"additional","affiliation":[{"name":"Immunology and inflammation Program, Garvan Institute of Medical Research , Darlinghurst, New South Wales,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliana","family":"Mari\u00f1o","sequence":"additional","affiliation":[{"name":"Immunology and inflammation Program, Garvan Institute of Medical Research , Darlinghurst, New South Wales,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Thaxton","sequence":"additional","affiliation":[{"name":"Immunology and inflammation Program, Garvan Institute of Medical Research , Darlinghurst, New South Wales,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Weinberg","sequence":"additional","affiliation":[{"name":"Immunology and inflammation Program, Garvan Institute of Medical Research , Darlinghurst, New South Wales,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabienne","family":"Mackay","sequence":"additional","affiliation":[{"name":"Immunology and inflammation Program, Garvan Institute of Medical Research , Darlinghurst, New South Wales,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Brink","sequence":"additional","affiliation":[{"name":"Immunology and inflammation Program, Garvan Institute of Medical Research , Darlinghurst, New South Wales,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathon","family":"Sprent","sequence":"additional","affiliation":[{"name":"Immunology and inflammation Program, Garvan Institute of Medical Research , Darlinghurst, New South Wales,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shane T","family":"Grey","sequence":"additional","affiliation":[{"name":"Immunology and inflammation Program, Garvan Institute of Medical Research , Darlinghurst, New South Wales,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,1,15]]},"reference":[{"key":"2026012806214990000_R1","first-page":"243","article-title":"The BAFF\/APRIL system: an important player in systemic rheumatic diseases.","volume-title":"Curr. Dir. Autoimmun.","year":"2005"},{"key":"2026012806214990000_R2","first-page":"1453","article-title":"BAFF mediates survival of peripheral immature B lymphocytes.","volume-title":"J. Exp. Med.","year":"2000"},{"key":"2026012806214990000_R3","first-page":"2111","article-title":"An essential role for BAFF in the normal development of B cells through a BCMA-independent pathway.","volume-title":"Science","year":"2001"},{"key":"2026012806214990000_R4","first-page":"138","article-title":"NF-AT activation induced by a CAML-interacting member of the tumor necrosis factor receptor superfamily.","volume-title":"Science","year":"1997"},{"key":"2026012806214990000_R5","first-page":"807","article-title":"B cell-activating factor belonging to the TNF family (BAFF)-R is the principal BAFF receptor facilitating BAFF costimulation of circulating T and B cells.","volume-title":"J. Immunol.","year":"2004"},{"key":"2026012806214990000_R6","first-page":"2750","article-title":"BAFF binding to T cell-expressed BAFF-R costimulates T cell proliferation and alloresponses.","volume-title":"Eur. J. Immunol.","year":"2004"},{"key":"2026012806214990000_R7","first-page":"252","article-title":"APRIL and TALL-I and receptors BCMA and TACI: system for regulating humoral immunity.","volume-title":"Nat. Immunol.","year":"2000"},{"key":"2026012806214990000_R8","first-page":"467","article-title":"BAFF production by antigen-presenting cells provides T cell co-stimulation.","volume-title":"Int. Immunol.","year":"2004"},{"key":"2026012806214990000_R9","first-page":"5537","article-title":"BAFF augments certain Th1-associated inflammatory responses.","volume-title":"J. Immunol.","year":"2005"},{"key":"2026012806214990000_R10","first-page":"2245","article-title":"TNF family member B cell-activating factor (BAFF) receptor-dependent and -independent roles for BAFF in B cell physiology.","volume-title":"J. Immunol.","year":"2004"},{"key":"2026012806214990000_R11","first-page":"1697","article-title":"Mice transgenic for BAFF develop lymphocytic disorders along with autoimmune manifestations.","volume-title":"J. Exp. Med.","year":"1999"},{"key":"2026012806214990000_R12","first-page":"329","article-title":"Regulatory T cell lineage specification by the forkhead transcription factor foxp3.","volume-title":"Immunity.","year":"2005"},{"key":"2026012806214990000_R13","first-page":"958","article-title":"BAFF-induced NEMO-independent processing of NF-\u03baB2 in maturing B cells.","volume-title":"Nat. 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Immunol.","year":"2002"},{"key":"2026012806214990000_R19","first-page":"600","article-title":"A role for CD45RBlowCD38+ T cells and costimulatory pathways of T-cell activation in protection of non-obese diabetic (NOD) mice from diabetes.","volume-title":"Immunology","year":"1999"},{"key":"2026012806214990000_R20","first-page":"2808","article-title":"Regulated compartmentalization of programmed cell death-1 discriminates CD4+CD25+ resting regulatory T cells from activated T cells.","volume-title":"J. Immunol.","year":"2006"},{"key":"2026012806214990000_R21","first-page":"303","article-title":"Developmental stage, phenotype, and migration distinguish naive- and effector\/memory-like CD4+ regulatory T cells.","volume-title":"J. Exp. Med.","year":"2004"},{"key":"2026012806214990000_R22","first-page":"240","article-title":"Characterization of peripheral regulatory CD4+ T cells that prevent diabetes onset in nonobese diabetic mice.","volume-title":"J. 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Immunol.","year":"2005"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/182\/2\/793\/62680435\/8380.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/182\/2\/793\/62680435\/8380.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T11:22:04Z","timestamp":1769599324000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/182\/2\/793\/8004403"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,1]]},"references-count":25,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2009,1,15]]},"published-print":{"date-parts":[[2009,1,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.182.2.793","relation":{},"ISSN":["1550-6606","0022-1767"],"issn-type":[{"value":"1550-6606","type":"electronic"},{"value":"0022-1767","type":"print"}],"subject":[],"published-other":{"date-parts":[[2009,1]]},"published":{"date-parts":[[2009,1]]}}}