title: Mechanism of the immunosuppressive effect in vivo of novel immunosuppressive drug beta-SQAG9, which inhibits the response of the CD62L+ T-cell subset.
abstract: BACKGROUND
  We synthesized sulfo-glycolipid, beta-SQAG9 (designate square beta-SQAG9 liposome, because it efficiently forms a liposome structure) that possessed immunosuppressive effects such as inhibition of T-cell responses in human allogeneic MLR and skin allograft survival in rats, and bound to CD62L (L-selectin) in vitro. In this study, we further investigated the immunosuppressive mechanism in vivo by beta-SQAG9 liposome in a skin-allografted rat model.
  
  
  METHODS
  ACI rats (RT1(a)) were grafted skin of LEW rats (RT1(1)) treated with PBS or beta-SQAG9 liposome IV once a day for 7 days. Subsequently, we investigated the population of T cells and CD62L(+) T-cell subset in the spleen, axillary lymph nodes (ALNs), and peripheral blood of skin-allografted rats by two-color flow cytometry.
  
  
  RESULTS
  Five of 11 (45.5%) rats that were treated with 50 mg/kg beta-SQAG9 liposome showed graft survival and another showed moderate rejection in graft. The CD62L(+) T-cell subset population in ALNs of beta-SQAG9 liposome-treated rats decreased in a dose-dependent manner. No significant difference in the T-cell population was observed between the beta-SQAG9 and control groups. These data suggest that beta-SQAG9 could bind to the CD62L(+) T-cell subset in vivo as well as in vitro and affect T-cell migration, which might lead to T-cell tolerance in vivo.
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Takenouchi
authors.forename: H
authors.initials: H
authors.lastname: Sahara
authors.forename: Y
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: A
authors.initials: A
authors.lastname: Imai
authors.forename: T
authors.initials: T
authors.lastname: Fujita
authors.forename: Y
authors.initials: Y
authors.lastname: Tamura
authors.forename: N
authors.initials: N
authors.lastname: Takahashi
authors.forename: S
authors.initials: S
authors.lastname: Gasa
authors.forename: K
authors.initials: K
authors.lastname: Matsumoto
authors.forename: K
authors.initials: K
authors.lastname: Ohta
authors.forename: F
authors.initials: F
authors.lastname: Sugawara
authors.forename: K
authors.initials: K
authors.lastname: Sakaguchi
authors.forename: K
authors.initials: K
authors.lastname: Jimbow
authors.forename: N
authors.initials: N
authors.lastname: Sato
mesh_terms: D000818:Animals; D006017:Glycolipids / Q000494:pharmacology*; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D019041:L-Selectin / Q000187:drug effects / Q000276:immunology*; D008081:Liposomes; D023421:Models, Animal; D051381:Rats; D011912:Rats, Inbred ACI; D011917:Rats, Inbred Lew; D016038:Skin Transplantation / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
chemical_list: D006017:Glycolipids; D007166:Immunosuppressive Agents; D008081:Liposomes; C496611:sulfoquinovosylacylglycerol; D019041:L-Selectin