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 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.
Soos
J M
JM
Center for Neurologic Diseases, Harvard Institutes of Medicine, Boston, MA 02115, USA.
Ashley
T A
TA
Morrow
J
J
Patarroyo
J C
JC
Szente
B E
BE
Zamvil
S S
SS
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000382:microbiology; D015703:Antigens, CD / Q000096:biosynthesis* / Q000276:immunology; D001253:Astrocytes / Q000276:immunology* / Q000378:metabolism*; D018122:B7-1 Antigen / Q000096:biosynthesis* / Q000276:immunology*; D051940:B7-2 Antigen; D018106:CD28 Antigens / Q000276:immunology / Q000378:metabolism; D002461:Cell Line, Transformed; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000276:immunology; D051379:Mice; D004676:Myelin Basic Protein / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000382:microbiology
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; C497965:Cd86 protein, mouse; D016207:Cytokines; D008562:Membrane Glycoproteins; D004676:Myelin Basic Protein; D007371:Interferon-gamma