Differential expression of B7 co-stimulatory molecules by astrocytes correlates with T cell activation and cytokine production

Whether astrocytes utilize B7:CD28 co-stimulation to activate T cells media ting CNS inflammatory disease is controversial In this report, primary astr ocytes and murine astrocyte lines, generated by immortalization at two diff erent times, day 7 or 45 of culture, were examined for their capability to express B7 co-stimulatory molecules and to participate in B7:CD28 co-stimul ation. Following exposure to IFN-gamma, primary astrocytes and astrocyte li nes up-regulated MHC class II and B7-2 (CD86) molecules. However, B7-1 (CD8 0) expression was not inducible on primary astrocytes examined after IFN-ga mma stimulation beginning on day 7 or on astrocyte lines immortalized on da y 7, B7-1 expression was inducible on primary astrocytes examined later and could be up-regulated on astrocyte lines immortalized later. Unlike B7-1, temporal discordant expression of other co-stimulatory/adhesion molecules w as not observed. Both B7-1(-)/B7-2(+) and B7-1(+)/B7-2(+) astrocyte lines w ere capable of stimulating proliferation of encephalitogenic T(h)1 cells, u tilizing B7-2 for B7:CD28 co-stimulation, However, lines derived from immor talization later (B7-1(+)/B7-2(+)) were more effective in stimulating proli feration of naive myelin basic protein-specific CD4(+) T cells. Astrocyte l ines that expressed both B7-1 and B7-2 also stimulated Thp cells to secrete proinflammatory T(h)1 cytokines, whereas lines that expressed B7-2 only st imulated Thp cells to produce a T(h)2 cytokine pattern. Thus, we demonstrat e for the first time that individual astrocytes can differentially express B7-1 molecules, which may correlate with their ability to stimulate proinfl ammatory and regulatory patterns of cytokine production. These results sugg est that astrocytes have potential for both promoting and down-regulating T cell responses, and that temporal differences in expression of B7 molecule s should be considered when evaluating immune regulation by astrocytes.