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However, whether in vivo expansion of endogenous Tregs can downregulate CHS-mediated inflammation remains to be elucidated. In this study, we addressed this issue by using injection of an IL-2\/anti\u2013IL-2 mAb JES6-1 complex (IL-2\/JES6-1) as a means of Treg induction in 2,4,6-trinitrochlorobenzene\u2013induced CHS. IL-2\/JES6-1 injection before or after hapten sensitization led to a considerable reduction of skin inflammation, even when rechallenged up to 3 wk after the last treatment. Conversely, Treg depletion re-established the CHS response in IL-2\/JES6-1\u2013treated mice. IL-2\/JES6-1 injection resulted in increased frequencies of natural and peripheral Tregs in spleen and draining lymph nodes (LNs), elevated IL-10 and TGF-\u03b2 production by CD4 T cells, reduced CD86 expression by dendritic cells, and led to lower numbers of hapten-specific IFN-\u03b3\u2013producing CD8 T effector cells in LNs. Neutrophil and CD8 T cell infiltration was reduced in inflamed ear tissue, whereas CTLA-4+Foxp3+ Treg frequencies were augmented. Adoptive transfer of LN cells of sensitized mice into recipients treated with IL-2\/JES6-1 showed impaired CHS. Our results show that in vivo Treg expansion results in a prolonged CHS suppression, a sustained reduction of hapten-specific CD8 T cells, and a decrease in effector cell influx in inflamed tissue.<\/jats:p>","DOI":"10.4049\/jimmunol.1600508","type":"journal-article","created":{"date-parts":[[2016,7,21]],"date-time":"2016-07-21T02:39:14Z","timestamp":1469068754000},"page":"1567-1576","source":"Crossref","is-referenced-by-count":17,"title":["In Vivo Expansion of Endogenous Regulatory T Cell Populations Induces Long-Term Suppression of Contact Hypersensitivity"],"prefix":"10.1093","volume":"197","author":[{"given":"Asmaa","family":"El Beidaq","sequence":"first","affiliation":[{"name":"Institute for Systemic Inflammation Research, University of L\u00fcbeck , 23538 L\u00fcbeck,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher W M","family":"Link","sequence":"additional","affiliation":[{"name":"Institute for Systemic Inflammation Research, University of L\u00fcbeck , 23538 L\u00fcbeck,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharina","family":"Hofmann","sequence":"additional","affiliation":[{"name":"Institute for Systemic Inflammation Research, University of L\u00fcbeck , 23538 L\u00fcbeck,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Britta","family":"Frehse","sequence":"additional","affiliation":[{"name":"Institute for Systemic Inflammation Research, University of L\u00fcbeck , 23538 L\u00fcbeck,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin","family":"Hartmann","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of L\u00fcbeck , 23538 L\u00fcbeck,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3855-6683","authenticated-orcid":false,"given":"Katja","family":"Bieber","sequence":"additional","affiliation":[{"name":"L\u00fcbeck Institute of Experimental Dermatology, University of L\u00fcbeck , 23538 L\u00fcbeck,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1617-1280","authenticated-orcid":false,"given":"Stefan F","family":"Martin","sequence":"additional","affiliation":[{"name":"Allergy Research Group, Department of Dermatology, Medical Center, University of Freiburg , 79104 Freiburg,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralf J","family":"Ludwig","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of L\u00fcbeck , 23538 L\u00fcbeck,","place":["Germany"]},{"name":"L\u00fcbeck Institute of Experimental Dermatology, University of L\u00fcbeck , 23538 L\u00fcbeck,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1263-7693","authenticated-orcid":false,"given":"Rudolf A","family":"Manz","sequence":"additional","affiliation":[{"name":"Institute for Systemic Inflammation Research, University of L\u00fcbeck , 23538 L\u00fcbeck,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2016,9,1]]},"reference":[{"key":"2025030617481172800_r1","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1097\/ACI.0000000000000142","article-title":"Immunological mechanisms in allergic contact dermatitis","volume":"15","author":"Martin","year":"2015","journal-title":"Curr. 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