title: CD8+CD122+ regulatory T cells (Tregs) and CD4+ Tregs cooperatively prevent and cure CD4+ cell-induced colitis.
abstract: We identified CD8(+)CD122(+) regulatory T cells (Tregs) and demonstrated their importance in the maintenance of immune homeostasis and in the recovery from experimental autoimmune encephalomyelitis. In this paper, we show that CD8(+)CD122(+) Tregs effectively prevent and cure colitis in a mouse model. In our experiments, colitis was induced in lymphocyte-deficient RAG-2(-/-) mice by transferring CD4(+)CD45RB(high) cells that were excluded with CD4(+) Tregs. Cotransfer of CD8(+)CD122(+) cells clearly suppressed the development of colitis, and this suppressive effect was similar to that of CD4(+)CD45RB(low) cells that were mostly CD4(+) Tregs. CD8(+)CD122(+) cells obtained from IL-10(-/-) mice were unable to suppress colitis, indicating that IL-10 is an important effect-transmitting factor in the suppression of colitis. CD8(+)CD122(+) cells showed a suppressive effect when they were transferred 4 wk after CD4(+)CD45RB(high) cells, indicating the therapeutic potential of CD8(+)CD122(+) cells. A mixture of CD8(+)CD122(+) cells and CD4(+)CD45RB(low) cells was far more effective than single Tregs, indicating the synergistic effect of these Tregs. These overall findings demonstrate the potential role of CD8(+) Tregs, and possibly together with CD4(+) Tregs, in the medical care of inflammatory bowel disease patients.
authors.affiliation: Department of Immunology, Nagoya University Graduate School of Medicine, Japan.
authors.forename: Agustina Tri
authors.initials: AT
authors.lastname: Endharti
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Okuno
authors.forename: Zhe
authors.initials: Z
authors.lastname: Shi
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Misawa
authors.forename: Shinya
authors.initials: S
authors.lastname: Toyokuni
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ito
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Isobe
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Suzuki
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D002450:Cell Communication / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D003092:Colitis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics; D053646:Interleukin-2 Receptor beta Subunit / Q000008:administration & dosage / Q000096:biosynthesis* / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000096:biosynthesis / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology / Q000637:transplantation
chemical_list: D053646:Interleukin-2 Receptor beta Subunit; D016753:Interleukin-10; D017493:Leukocyte Common Antigens