Inhibition of CD62L+ T-cell response in vitro via a novel sulfo-glycolipid, β-SQAG9 liposome that binds to CD62L molecule on the cell surface

We previously reported that synthetic sulfo-glycolipid, 3-O-(6-deoxy-6-sulfono-beta-D-glucopyranosyl)-1,2-di-O-acylglycerol (beta-SQDG(18:0)) which was deduced from sulfonoquinovosyl-diacylglycerols of sea urchin possessed immunosuppressive effects, such as human mixed lymphocyte reaction (MLR) and skin allograft in rat, and that these effects were caused by contact inhibition between T-cells and antigen presenting cells (APCs). Here, we investigated the mechanism of these immunosuppressive effects on human MLR by beta-SQAG9 which had been newly synthesized from beta-SQDG(18:0) to improve structural stability in water solution. CD62L(+) T-cells in peripheral blood predominantly respond to APCs, and beta-SQAG9 inhibited the response of CD62L(+) T-cell subset in human allogencic MLR. Surprisingly, it was demonstrated that P-SQAG9 bound to L- and P-selectin (CD62L and P) molecule in vitro. Meanwhile, P-SQAG9 efficiently formed liposome structure and bound to L-selectin on the cell surface of CD62L(+) T-cell subset but might not be incorporated into the cells. Because the immunosuppressive effects of P-SQAG9 disappeared when P-SQAG9 liposome was changed to soluble form by detergent, the liposome structure of P-SQAG9 was presumed to be essential for these effects. These findings suggested P-SQAG9 to be a novel drug with a unique immunosuppressive action. (c) 2005 Elsevier Inc. All rights reserved.