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. 2002 Nov 11;25(2):209–219. doi: 10.1016/0165-5728(89)90139-2

Tumor necrosis factor-α enhances interferon-γ-mediated class II antigen expression on astrocytes

Etty N Benveniste 1,2,∗, Shaun M Sparacio 1, John R Bethea 2
PMCID: PMC7119699  PMID: 2555395

Abstract

Astrocytes can function as antigen-presenting cells (APC) upon expression of class II antigens, which are induced by interferon-γ (IFN-γ). Tumor necrosis factor-α (TNF-α) can act synergistically with IFN-γ with respect to class II expression on a variety of cells. As brain cells themselves can secrete TNF-like factors upon stimulation, we examined the effect of TNF-α on IFN-γ-mediated class II induction on astrocytes. TNF-α alone had no effect on class II expression, but did synergize with IFN-γ for enhanced expression of class II antigens. The specificity of TNF-α activity was demonstrated by blocking the amplifying effect of TNF-α with a polyclonal anti-TNF-α antibody. Kinetic analysis of the synergistic effect indicated that optimal TNF-α enhancement of class II expression was observed when astrocytes were pretreated with IFN-γ 12–24 h prior to TNF-α addition. A possible mechanism for the synergistic action between IFN-γ and TNF-α may be increased TNF-α receptor expression by IFN-γ. Astrocytes treated with IFN-γ for 24 h express more TNF-α receptors (3900/cell) than do untreated astrocytes (2483/cell), with no significant change in the binding affinity (Kd). These results suggest that the synergistic activity of TNF-α requires an inductive signal from IFN-γ, which in part may be increased TNF-α receptor expression. Altogether, our observations indicate that TNF-α enhances ongoing class II major histocompatibility complex gene expression in rat astrocytes, which in this system is initially induced by IFN-γ. TNF-α exerts its effect by binding to high affinity TNF-α receptors on astrocytes, whose expression is also enhanced by IFN-γ. These two cytokines work in concert to elevate class II expression on astrocytes, an event which can contribute to initiation and/or perpetuation of intracerebral immune responses.

Keywords: Astrocyte, Major histocompatibility complex, Tumor necrosis factor, Interferon-γ

Abbreviations: APC, antigen-presenting cell; BBB, blood-brain barrier; CNS, central nervous system; GFAP, glial fibrillary acidic protein; IFN-γ, interferon-γ; IL-1, interleukin-1; MHC, major histocompatibility complex; MS, multiple sclerosis; TNF-α, tumor necrosis factor-α

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