start-ver=1.4 cd-journal=joma no-vol=156 cd-vols= no-issue=1-2 article-no= start-page=82 end-page=93 dt-received= dt-revised= dt-accepted= dt-pub-year=2013 dt-pub=201312 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=IL-7 promotes long-term in vitro survival of unique long-lived memory subset generated from mucosal effector memory CD4(+) T cells in chronic colitis mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Colitogenic memory CD4(+) T cells are important in the pathogenesis of inflammatory bowel disease (IBD). Although memory stem cells with high survival and self-renewal capacity were recently identified in both mice and humans, it is unclear whether a similar subset is present in chronic colitis mice. We sought to identify and purify a long-lived subset of colitogenic memory CD4(+) T cells, which may be targets for treatment of IBD. A long-lived subset of colitogenic memory CD4(+) T cells was purified using a long-term culture system. The characteristics of these cells were assessed. Interleukin (IL)-7 promoted the in vitro survival for >8 weeks of lamina propria (LP) CD4(+) T cells from colitic SOD mice previously injected with CD4(+)CD45RB(high) T cells. These cells were in a quiescent state and divided a maximum of 5 times in 4 weeks. LP CD4(+) T cells expressed higher levels of Bcl-2, integrin-alpha 4 beta 7, CXCR3 and CD25 after than before culture, as well as secreting high concentrations of IL-2 and low concentrations of IFN-gamma and IL-17 in response to intestinal bacterial antigens. LP CD4(+) T cells from colitic mice cultured with IL-7 for 8 weeks induced more severe colitis than LP CD4(+) T cells cultured for 4 weeks. We developed a novel culture system to purify a long-lived, highly pathogenic memory subset from activated LP CD4(+) T cells. IL-7 promoted long-term in vitro survival of this subset in a quiescent state. This subset will be a novel, effective target for the treatment of IBD. en-copyright= kn-copyright= en-aut-name=TakaharaMasahiro en-aut-sei=Takahara en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NemotoYasuhiro en-aut-sei=Nemoto en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OshimaShigeru en-aut-sei=Oshima en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsuzawaYu en-aut-sei=Matsuzawa en-aut-mei=Yu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KanaiTakanori en-aut-sei=Kanai en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkamotoRyuichi en-aut-sei=Okamoto en-aut-mei=Ryuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TsuchiyaKiichiro en-aut-sei=Tsuchiya en-aut-mei=Kiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakamuraTetsuya en-aut-sei=Nakamura en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamamotoKazuhide en-aut-sei=Yamamoto en-aut-mei=Kazuhide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=WatanabeMamoru en-aut-sei=Watanabe en-aut-mei=Mamoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil= kn-affil=Tokyo Med & Dent Univ, Dept Gastroenterol & Hepatol, Grad Sch affil-num=2 en-affil= kn-affil=Tokyo Med & Dent Univ, Dept Gastroenterol & Hepatol, Grad Sch affil-num=3 en-affil= kn-affil=Tokyo Med & Dent Univ, Dept Gastroenterol & Hepatol, Grad Sch affil-num=4 en-affil= kn-affil=Tokyo Med & Dent Univ, Dept Gastroenterol & Hepatol, Grad Sch affil-num=5 en-affil= kn-affil=Keio Univ, Dept Internal Med, Div Gastroenterol & Hepatol, Sch Med affil-num=6 en-affil= kn-affil=Tokyo Med & Dent Univ, Dept Gastroenterol & Hepatol, Grad Sch affil-num=7 en-affil= kn-affil=Tokyo Med & Dent Univ, Dept Gastroenterol & Hepatol, Grad Sch affil-num=8 en-affil= kn-affil=Tokyo Med & Dent Univ, Dept Gastroenterol & Hepatol, Grad Sch affil-num=9 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Gastroenterol & Hepatol affil-num=10 en-affil= kn-affil=Tokyo Med & Dent Univ, Dept Gastroenterol & Hepatol, Grad Sch en-keyword=Inflammatory bowel disease kn-keyword=Inflammatory bowel disease en-keyword=Memory T cells kn-keyword=Memory T cells en-keyword=CD4 kn-keyword=CD4 en-keyword=IL-7 kn-keyword=IL-7 en-keyword=Cell culture kn-keyword=Cell culture END