gamma delta T-cell-human glial cell interactions. I. In vitro induction of gammadelta T-cell expansion by human glial cells.

gamma delta T-cells are found in increased proportion in multiple sclerosis (MS) white matter plaque infiltrates compared with peripheral blood or spleen, raising the possibility that they are either specifically attracted to lesion sites or, once present, are stimulated to expand. We have previously shown that human oligodendrocytes (OGC) preferentially express heat shock proteins (hsp), molecules to which gamma delta T-cells have been known to react and that in vitro expanded gamma delta T-cells can lyse OGC. We therefore investigated whether human glial cells, that differentially express hsp, could stimulate gamma delta T-cell expansion from peripheral blood. We compared the glial cell-induced expansion to cell lines which also differentially express hsp and have been shown to selectively stimulate gamma delta T-cell expansion (e.g. RPMI 8226, Daudi). We found that both OGC and human fetal astrocytes (hFA) expressed hsp and stimulated the preferential expansion of gamma delta T-cells to about the same extent as the hsp expressing cell lines RPMI 8226 or Daudi, in the presence of exogenous interleukin-2 (IL-2) but without any T-cell mitogen. Furthermore, the type of gamma delta T-cells expanded were of the V delta 2 subtype known to be particularly reactive to hsp. Microglia, U937 cell lines or purified myelin membranes, which express little or no hsp, did not support gamma delta T-cell growth. These results therefore suggest that OGC may contribute to the local expansion of gamma delta T-cells within MS plaques. Potential harmful effects of gamma delta T-cells on OGC may thereby contribute to the immunopathogenesis of MS demyelination.