International Immunology, Vol. 11, No. 7, 1169-1179,
July 1999
© 1999 Japanese Society for Immunology
Differential expression of B7 co-stimulatory molecules by astrocytes correlates with T cell activation and cytokine production
Center for Neurologic Diseases, Harvard Institutes of Medicine, and
1 Vascular Research Division, Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA
2 Department of Neurology, C-440, University of California, San Francisco, 521 Parnassus Avenue, San Francisco, CA 94143-0114, USA
Correspondence to: S. S. Zamvil as above; Email: zamvil{at}itsa.ucsf.edu
Whether astrocytes utilize B7:CD28 co-stimulation to activate T cells mediating CNS inflammatory disease is controversial. In this report, primary astrocytes and murine astrocyte lines, generated by immortalization at two different 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-stimulation. Following exposure to IFN-
, primary astrocytes and astrocyte lines up-regulated MHC class II and B7-2 (CD86) molecules. However, B7-1 (CD80) expression was not inducible on primary astrocytes examined after IFN- stimulation beginning on day 7 or on astrocyte lines immortalized on day 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 was not observed. Both B7-1–/B7-2+ and B7-1+/B7-2+ astrocyte lines were capable of stimulating proliferation of encephalitogenic Th1 cells, utilizing B7-2 for B7:CD28 co-stimulation. However, lines derived from immortalization later (B7-1+/B7-2+) were more effective in stimulating proliferation of naive myelin basic protein-specific CD4+ T cells. Astrocyte lines that expressed both B7-1 and B7-2 also stimulated Thp cells to secrete proinflammatory Th1 cytokines, whereas lines that expressed B7-2 only stimulated Thp cells to produce a Th2 cytokine pattern. Thus, we demonstrate for the first time that individual astrocytes can differentially express B7-1 molecules, which may correlate with their ability to stimulate proinflammatory and regulatory patterns of cytokine production. These results suggest that astrocytes have potential for both promoting and down-regulating T cell responses, and that temporal differences in expression of B7 molecules should be considered when evaluating immune regulation by astrocytes.
Keywords: antigen presentation, astrocytes, costimulation, experimental allergic encephalomyelitis, MHC class II, multiple sclerosis, T cells
Transmitting editor: L. Steinman
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