Mechanism of the immunosuppressive effect in vivo of novel immunosuppressive drug beta-SQAG9, which inhibits the response of the CD62L+ T-cell subset.
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.
Takenouchi
M
M
Department of Pathology, Sapporo Medical University School of Medicine, Japan.
Sahara
H
H
Yamamoto
Y
Y
Matsumoto
Y
Y
Imai
A
A
Fujita
T
T
Tamura
Y
Y
Takahashi
N
N
Gasa
S
S
Matsumoto
K
K
Ohta
K
K
Sugawara
F
F
Sakaguchi
K
K
Jimbow
K
K
Sato
N
N
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*
D006017:Glycolipids; D007166:Immunosuppressive Agents; D008081:Liposomes; C496611:sulfoquinovosylacylglycerol; D019041:L-Selectin