{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T01:44:00Z","timestamp":1791423840570,"version":"4.3.3"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2009,3,1]],"date-time":"2009-03-01T00:00:00Z","timestamp":1235865600000},"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":[[2009,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Tolerogenic dendritic cells (DC) play an important role in maintaining peripheral T cell tolerance in steady-state conditions through induction of anergic, IL-10-producing T cells with suppressive properties. ICOS, an activation-induced member of the CD28 family on T cells, is involved in the induction of IL-10, which itself could contribute to induction of anergy and development of suppressive T cells. Therefore, we analyzed the functional role of ICOS in the differentiation process of human CD4+ T cells upon their interaction with tolerogenic DC. We compared the functional properties of CD4+ T cells from healthy volunteers and ICOS-deficient patients after stimulation with tolerogenic DC. We report that induction of T cell anergy and suppressive capacity is completely blocked after knockdown of ICOS expression in T cells as well as after blocking of ICOS-ICOS ligand interaction in DC\/T cell cocultures. Moreover, CD4+ T cells from ICOS-deficient patients were completely resistant to anergy induction and differentiation into suppressive T cells even after supplementation of IL-10. Furthermore, ICOS\/ICOS ligand interaction stabilizes IL-10R expression on T cells and thus renders them sensitive to IL-10 effects. Taken together, these results indicate a crucial role for ICOS in the induction of peripheral tolerance maintained by tolerogenic DC mediated mostly via an IL-10-independent mechanism.<\/jats:p>","DOI":"10.4049\/jimmunol.0802733","type":"journal-article","created":{"date-parts":[[2009,3,5]],"date-time":"2009-03-05T20:01:20Z","timestamp":1236283280000},"page":"3349-3356","source":"Crossref","is-referenced-by-count":85,"title":["The Role of ICOS in Directing T Cell Responses: ICOS-Dependent Induction of T Cell Anergy by Tolerogenic Dendritic Cells"],"prefix":"10.1093","volume":"182","author":[{"given":"Andrea","family":"Tuettenberg","sequence":"first","affiliation":[{"name":"Department of Dermatology, University of Mainz , Mainz,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Huter","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Mainz , Mainz,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Hubo","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Mainz , Mainz,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Horn","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, University of Freiburg , Freiburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Knop","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Mainz , Mainz,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bodo","family":"Grimbacher","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, University of Freiburg , Freiburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A","family":"Kroczek","sequence":"additional","affiliation":[{"name":"Molecular Immunology, Robert Koch Institute , Berlin,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Stoll","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Mainz , Mainz,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmut","family":"Jonuleit","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Mainz , Mainz,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,3,15]]},"reference":[{"key":"2026012807050579900_R1","first-page":"411","article-title":"The induction of tolerance by dendritic cells that have captured apoptotic cells.","volume-title":"J. Exp. Med.","year":"2000"},{"key":"2026012807050579900_R2","first-page":"394","article-title":"Dendritic cells as a tool to induce anergic and regulatory T cells.","volume-title":"Trends Immunol.","year":"2001"},{"key":"2026012807050579900_R3","first-page":"1213","article-title":"Induction of interleukin 10-producing, nonproliferating CD4+ T cells with regulatory properties by repetitive stimulation with allogeneic immature human dendritic cells.","volume-title":"J. Exp. Med.","year":"2000"},{"key":"2026012807050579900_R4","first-page":"F5","article-title":"Differentiation of T regulatory cells by immature dendritic cells.","volume-title":"J. Exp. Med.","year":"2001"},{"key":"2026012807050579900_R5","first-page":"1162","article-title":"Differentiation of Tr1 cells by immature dendritic cells requires IL-10 but not CD25+CD4+ Tr cells.","volume-title":"Blood.","year":"2005"},{"key":"2026012807050579900_R6","first-page":"263","article-title":"ICOS is an inducible T cell costimulator structurally and functionally related to CD28.","volume-title":"Nature","year":"1999"},{"key":"2026012807050579900_R7","first-page":"827","article-title":"T cell costimulation through B7RP-1 and ICOS.","volume-title":"Nature","year":"1999"},{"key":"2026012807050579900_R8","first-page":"181","article-title":"Expression of ICOS in vivo defines CD4+ effector T cells with high inflammatory potential and a strong bias for secretion of interleukin 10.","volume-title":"J. Exp. Med.","year":"2003"},{"key":"2026012807050579900_R9","first-page":"2680","article-title":"ICOS and CD28 reversely regulate IL-10 on reactivation of human effector T cells with mature dendritic cells.","volume-title":"Eur. J. Immunol.","year":"2002"},{"key":"2026012807050579900_R10","first-page":"234","article-title":"ICOS deficiency in patients with common variable immunodeficiency.","volume-title":"Clin. Immunol.","year":"2004"},{"key":"2026012807050579900_R11","first-page":"3045","article-title":"Human ICOS deficiency abrogates the germinal center reaction and provides a monogenic model for common variable immunodeficiency.","volume-title":"Blood","year":"2006"},{"key":"2026012807050579900_R12","first-page":"1479","article-title":"CD4+CD25+ T regulatory cells dependent on ICOS promote regulation of effector cells in the prediabetic lesion.","volume-title":"J. Exp. Med.","year":"2004"},{"key":"2026012807050579900_R13","first-page":"1024","article-title":"Antigen-specific regulatory T cells develop via the ICOS-ICOS-ligand pathway and inhibit allergen-induced airway hyperreactivity.","volume-title":"Nat. Med.","year":"2002"},{"key":"2026012807050579900_R14","first-page":"2047","article-title":"Impaired regulatory T cell response and enhanced atherosclerosis in the absence of inducible costimulatory molecule.","volume-title":"Circulation","year":"2006"},{"key":"2026012807050579900_R15","first-page":"4192","article-title":"Inducible costimulator-dependent IL-10 production by regulatory T cells specific for self-antigen.","volume-title":"Proc. Natl. Acad. Sci. USA","year":"2004"},{"key":"2026012807050579900_R16","first-page":"605","article-title":"Characterization of dendritic cells that induce tolerance and T regulatory 1 cell differentiation in vivo.","volume-title":"Immunity","year":"2003"},{"key":"2026012807050579900_R17","first-page":"105","article-title":"Plasmacytoid dendritic cells prime IL-10-producing T regulatory cells by inducible costimulator ligand.","volume-title":"J. Exp. Med.","year":"2007"},{"key":"2026012807050579900_R18","first-page":"605","article-title":"The costimulatory molecule ICOS plays an important role in the immunopathogenesis of EAE.","volume-title":"Nat. Immunol.","year":"2001"},{"key":"2026012807050579900_R19","first-page":"97","article-title":"ICOS costimulatory receptor is essential for T cell activation and function.","volume-title":"Nature","year":"2001"},{"key":"2026012807050579900_R20","first-page":"3135","article-title":"Proinflammatory cytokines and prostaglandins induce maturation of potent immunostimulatory dendritic cells under fetal calf serum-free conditions.","volume-title":"Eur. J. Immunol.","year":"1997"},{"key":"2026012807050579900_R21","first-page":"261","article-title":"Homozygous loss of ICOS is associated with adult-onset common variable immunodeficiency.","volume-title":"Nat. Immunol.","year":"2003"},{"key":"2026012807050579900_R22","first-page":"105","article-title":"ICOS is essential for effective T helper cell responses.","volume-title":"Nature","year":"2001"},{"key":"2026012807050579900_R23","first-page":"774","article-title":"ICOS controls the pool size of effector-memory and regulatory T cells.","volume-title":"J. Immunol.","year":"2008"},{"key":"2026012807050579900_R24","first-page":"317","article-title":"Epicutaneous immunization with autoantigenic peptides induces T suppressor cells that prevent experimental allergic encephalomyelitis.","volume-title":"Immunity","year":"2003"},{"key":"2026012807050579900_R25","first-page":"942","article-title":"Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival.","volume-title":"Nat. Med.","year":"2004"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/182\/6\/3349\/62723489\/8665.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/182\/6\/3349\/62723489\/8665.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T12:05:44Z","timestamp":1769601944000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/182\/6\/3349\/8007741"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,3]]},"references-count":25,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2009,3,15]]},"published-print":{"date-parts":[[2009,3,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.0802733","relation":{},"ISSN":["1550-6606","0022-1767"],"issn-type":[{"value":"1550-6606","type":"electronic"},{"value":"0022-1767","type":"print"}],"subject":[],"published-other":{"date-parts":[[2009,3]]},"published":{"date-parts":[[2009,3]]}}}