Transforming growth factor‐β2 down‐regulates HLA‐DR antigen expression on human malignant glioma cells

Transforming growth factor‐β (TGF‐β) is known to have a potent inhibitory influence on several immune functions. It has recently been demonstrated that TGF‐β2 is identical to the glioblastoma‐derived T cell suppressor factor (G‐TsF). In the present study, human malignant glioma cell lines were incubated with various concentrations of TGF‐β2. An optimal concentration of 1 ng/ml TGF‐β2 produced a partial but significant decrease of HLA‐DR (class II) surface antigen expression on glioma cells expressing this antigen, as well as decreased levels of HLA‐DR‐specific mRNA. The surface expression of other HLA‐related molecules, such as HLA‐ABC (class I) and β2‐microglobulin, was not influenced by TGF‐β2. The suppressive effect of TGF‐β2 on HLA‐DR expression, both at the surface antigenic and cytoplasmic mRNA levels, could be completely overcome by adding relatively high concentrations (500 U/ml) of interferon (1FN)‐γ to the culture system. However, TGF‐β2 inhibited the enhancement of HLA‐DR surface expression produced by low concentrations of IFN‐γ on some cells which initially did not express these antigens. These results show that TGF‐β2 can act as a regulator of HLA‐DR antigen expression on human glioma cells.