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NLM AIDSLINE
Differential expression of B7 co-stimulatory molecules by astrocytes correlates with T cell activation and cytokine production.
Soos JM; Ashley TA; Morrow J; Patarroyo JC; Szente BE; Zamvil SS; Center
November 30, 1999
Int Immunol. 1999 Jul;11(7):1169-79. Unique Identifier : AIDSLINE

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-gamma, 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-gamma 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.

JOURNAL ARTICLE Animal Antigen-Presenting Cells/IMMUNOLOGY/MICROBIOLOGY Antigens, CD/*BIOSYNTHESIS/IMMUNOLOGY Antigens, CD28/IMMUNOLOGY/METABOLISM Antigens, CD80/*BIOSYNTHESIS/*IMMUNOLOGY Astrocytes/*IMMUNOLOGY/*METABOLISM Cell Line, Transformed Cytokines/*BIOSYNTHESIS/IMMUNOLOGY Interferon Type II/BIOSYNTHESIS/IMMUNOLOGY Lymphocyte Transformation/*IMMUNOLOGY Membrane Glycoproteins/*BIOSYNTHESIS/IMMUNOLOGY Mice Myelin Basic Proteins/IMMUNOLOGY Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. T-Lymphocytes/*IMMUNOLOGY/*METABOLISM Th1 Cells/IMMUNOLOGY/METABOLISM Th2 Cells/IMMUNOLOGY/MICROBIOLOGY

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