Mechanism of the immunosuppressive effect in vivo of novel immunosuppressive drug beta-SQAG9, which inhibits the response of the CD62L+ T-cell subset

Transplant Proc. 2005 Jan-Feb;37(1):139-42. doi: 10.1016/j.transproceed.2004.12.204.

Abstract

Introduction: 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.

MeSH terms

  • Animals
  • Glycolipids / pharmacology*
  • Graft Survival / drug effects
  • Graft Survival / immunology*
  • Immunosuppressive Agents / pharmacology*
  • L-Selectin / drug effects
  • L-Selectin / immunology*
  • Liposomes
  • Models, Animal
  • Rats
  • Rats, Inbred ACI
  • Rats, Inbred Lew
  • Skin Transplantation / immunology*
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*

Substances

  • Glycolipids
  • Immunosuppressive Agents
  • Liposomes
  • sulfoquinovosylacylglycerol
  • L-Selectin