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IFN-gamma-activated primary murine astrocytes express B7 costimulatory molecules and prime naive antigen-specific T cells.

K M Nikcevich, K B Gordon, L Tan, S D Hurst, J F Kroepfl, M Gardinier, T A Barrett and S D Miller
J Immunol January 15, 1997, 158 (2) 614-621;
K M Nikcevich
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K B Gordon
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L Tan
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S D Hurst
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J F Kroepfl
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M Gardinier
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T A Barrett
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S D Miller
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Abstract

Astrocytes may serve as effectual APCs for T cell-mediated immune responses to myelin components during multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). Although astrocytes have been reported not to constitutively express MHC class II molecules, expression is up-regulated during active EAE and by in vitro incubation with IFN-gamma. Previous studies have reported that cytokine-activated astrocytes are able to activate Ag-specific previously activated T cells, but not naive alloreactive T cells. In the current study, we show that a subset of primary murine astrocytes constitutively expresses B7-2 molecules, as determined by FACS and PCR analyses, and up-regulates surface expression and mRNA levels of both B7-2 and B7-1 upon IFN-gamma stimulation. In contrast to earlier reports, we found that both untreated and IFN-gamma-treated astrocytes were able to stimulate proliferation of previously activated OVA-specific Th1 cells. In contrast, only IFN-gamma-treated astrocytes activated naive, transgenic OVA-specific T cells. Astrocyte-induced activation of both OVA-specific naive T cells and activated Th1 cells was dependent primarily on B7-2-mediated costimulation, as proliferation was inhibited by CTLA4-Ig and by anti-B7-2 mAbs. These results suggest that astrocytes in an inflammatory environment have the capacity to express the required MHC class II and B7 costimulatory molecules necessary for efficient activation of naive T cells. Since we have shown that T cells specific for endogenous myelin epitopes released during acute EAE play the major pathologic effector role in subsequent disease relapses (epitope spreading), astrocytes could play a role in the local activation and expansion of these responses.

  • Copyright © 1997 by American Association of Immunologists

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The Journal of Immunology
Vol. 158, Issue 2
15 Jan 1997
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IFN-gamma-activated primary murine astrocytes express B7 costimulatory molecules and prime naive antigen-specific T cells.
K M Nikcevich, K B Gordon, L Tan, S D Hurst, J F Kroepfl, M Gardinier, T A Barrett, S D Miller
The Journal of Immunology January 15, 1997, 158 (2) 614-621;

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IFN-gamma-activated primary murine astrocytes express B7 costimulatory molecules and prime naive antigen-specific T cells.
K M Nikcevich, K B Gordon, L Tan, S D Hurst, J F Kroepfl, M Gardinier, T A Barrett, S D Miller
The Journal of Immunology January 15, 1997, 158 (2) 614-621;
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Print ISSN 0022-1767        Online ISSN 1550-6606