Effect of HMG-CoA reductase inhibitors on activation of human γδT cells induced by Mycobacterium tuberculosis antigens

Abstract

Lipid rafts are cholesterol-enriched microdomains which act as a platform for the initiation of T-cell activation. To investigate effect of endogenous cholesterol on lipid rafts formation and activation of γδT cells, human peripheral blood mononuclear cells were stimulated in vitro with Mycobacterium tuberculosis antigens (Mtb-Ag). Lovastatin and fluvastatin, two 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (HMGCR) inhibitors, were used to block endogenous cholesterol biosynthesis. The expression of ganglioside GM1 (GM1), a lipid rafts marker, and CD69, an activation marker, and the level of tyrosine phosphorylation in γδT cells were measured by flow cytometry. The expression and aggregation of GM1 were also detected with laser confocal microscopy. We found that lovastatin and fluvastatin could obviously inhibit tyrosine phosphorylation and expression of GM1 and CD69 in γδT cells induced by Mtb-Ag. These results collectively indicated that HMGCR inhibitors might interfere with the formation of lipid rafts and inhibit the activation of γδT cells induced by Mtb-Ag.