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IFN-gamma-activated primary murine astrocytes express B7 costimulatory molecules and prime naive antigen-specific T cells.
Nikcevich, K M; Gordon, K B; Tan, L; Hurst, S D; Kroepfl, J F; Gardinier, M; Barrett, T A; Miller, S D.
Afiliación
  • Nikcevich KM; Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, IL 60611, USA.
J Immunol ; 158(2): 614-21, 1997 Jan 15.
Article en En | MEDLINE | ID: mdl-8992975
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.
Asunto(s)
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Colección: 01-internacional Asunto principal: Glicoproteínas de Membrana / Linfocitos T / Antígenos CD / Ovalbúmina / Astrocitos / Interferón gamma / Antígeno B7-1 / Inmunoconjugados Límite: Animals Idioma: En Revista: J Immunol Año: 1997 Tipo del documento: Article País de afiliación: Estados Unidos
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Colección: 01-internacional Asunto principal: Glicoproteínas de Membrana / Linfocitos T / Antígenos CD / Ovalbúmina / Astrocitos / Interferón gamma / Antígeno B7-1 / Inmunoconjugados Límite: Animals Idioma: En Revista: J Immunol Año: 1997 Tipo del documento: Article País de afiliación: Estados Unidos