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In this study, we demonstrate that LNSC subsets display distinct kinetics following vaccinia virus infection. In particular, compared with the expansion of other LNSC subsets and the total LN cell population, the expansion of fibroblastic reticular cells (FRCs) was delayed and sustained by noncirculating progenitor cells. Notably, newly generated FRCs were preferentially located in perivascular areas. Viral clearance in reactive LNs preceded the onset of FRC expansion, raising the possibility that viral infection in LNs may have a negative impact on the differentiation of FRCs. We also found that MHC class II expression was upregulated in all LNSC subsets until day 10 postinfection. Genetic ablation of radioresistant stromal cell\u2013mediated Ag presentation resulted in slower contraction of Ag-specific CD4+ T cells. We propose that activated LNSCs acquire enhanced Ag-presentation capacity, serving as an extrinsic brake system for CD4+ T cell responses. Disrupted function and homeostasis of LNSCs may contribute to immune deregulation in the context of chronic viral infection, autoimmunity, and graft-versus-host disease.<\/jats:p>","DOI":"10.4049\/jimmunol.1302946","type":"journal-article","created":{"date-parts":[[2014,7,15]],"date-time":"2014-07-15T04:13:20Z","timestamp":1405397600000},"page":"1636-1644","source":"Crossref","is-referenced-by-count":45,"title":["Lymph Node Stromal Cells Negatively Regulate Antigen-Specific CD4+ T Cell Responses"],"prefix":"10.1093","volume":"193","author":[{"given":"Jun","family":"Abe","sequence":"first","affiliation":[{"name":"Department of Molecular Preventive Medicine, Graduate School of Medicine, University of Tokyo , Tokyo 113-0033 ,","place":["Japan"]},{"name":"Japan Science and Technology Agency , Tokyo 102-8666 ,","place":["Japan"]},{"name":"Theodor Kocher Institute, University of Bern , CH-3012 Bern ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeyuki","family":"Shichino","sequence":"additional","affiliation":[{"name":"Department of Molecular Preventive Medicine, Graduate School of Medicine, University of Tokyo , Tokyo 113-0033 ,","place":["Japan"]},{"name":"Japan Science and Technology Agency , Tokyo 102-8666 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Ueha","sequence":"additional","affiliation":[{"name":"Department of Molecular Preventive Medicine, Graduate School of Medicine, University of Tokyo , Tokyo 113-0033 ,","place":["Japan"]},{"name":"Japan Science and Technology Agency , Tokyo 102-8666 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin-ichi","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Department of Molecular Preventive Medicine, Graduate School of Medicine, University of Tokyo , Tokyo 113-0033 ,","place":["Japan"]},{"name":"Japan Science and Technology Agency , Tokyo 102-8666 ,","place":["Japan"]},{"name":"Division of Nephrology, Department of Laboratory Medicine, Kanazawa University , Ishikawa 920-1192 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michio","family":"Tomura","sequence":"additional","affiliation":[{"name":"Center for Innovation in Immunoregulative Technology and Therapeutics, Graduate School of Medicine, Kyoto University , Kyoto 606-8501 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Inagaki","sequence":"additional","affiliation":[{"name":"Japan Science and Technology Agency , Tokyo 102-8666 ,","place":["Japan"]},{"name":"Center for Matrix Biology and Medicine, Graduate School of Medicine, Institute of Medical Sciences, Tokai University , Kanagawa 259-1143 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens V","family":"Stein","sequence":"additional","affiliation":[{"name":"Theodor Kocher Institute, University of Bern , CH-3012 Bern ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kouji","family":"Matsushima","sequence":"additional","affiliation":[{"name":"Department of Molecular Preventive Medicine, Graduate School of Medicine, University of Tokyo , Tokyo 113-0033 ,","place":["Japan"]},{"name":"Japan Science and Technology Agency , Tokyo 102-8666 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,8,15]]},"reference":[{"key":"2025030707290143300_r1","doi-asserted-by":"crossref","first-page":"10871","DOI":"10.1073\/pnas.0802278105","article-title":"Monitoring cellular movement in vivo with photoconvertible fluorescence protein \u201cKaede\u201d transgenic mice","volume":"105","author":"Tomura","year":"2008","journal-title":"Proc. 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