γδ T-cell–human glial cell interactions. II. Relationship between heat shock protein expression and susceptibility to cytolysis

Abstract

γ δ T-cells have been implicated in the immunopathogenesis of multiple sclerosis (MS), possibly through interaction with heat shock proteins ( hsp). We have previously demonstrated that human oligodendrocytes (OGC) express hsp on their surface and induce the proliferation and expansion of γ δ T-cells. We also showed that γ δ T-cells are highly cytolytic to OGC in vitro. The current study addresses whether γ δ T-cell-induced cytotoxicity to OGC involves the recognition of hsp on OGC or some other ligand. We first compared the lytic potential for different human glial cells and found that γ δ T-cells lysed OGC, microglia and human fetal astrocytes to the same extent, despite the preferential expression of hsp only on OGC. This suggested that either hsp was not involved in cytolytic recognition or that more than one ligand exists. To address this we used cell lines that either shared OGC properties of hsp expression and the ability to stimulate γ δ T-cells (RPMI 8226, Daudi) or did not (U937) in cold target competition assays with OGC. Results demonstrated that although all the cell lines were effectively killed by γ δ T-cells, only the RPMI 8226 and Daudi cells were able to effectively compete for lysis with the OGC. These results support the notion that probably more than one ligand for γ δ T-cell cytotoxic recognition exists but hsp could still be involved in γ δ T-cell-induced lysis of OGC. Regulating the expression of hsp on OGC might therefore be a way of interfering with potential γ δ T-cell-induced damage in MS.