Regulation of Fas and FasL expression on rat Schwann cells

Although the PNS belongs to the immune privileged sites, it can become a ta rget of immune attacks by invading T cells, causing inflammation and destru ction. Yet the PNS also has a protective potential by eliminating the infla mmatory cells via apoptosis. In analogy with other immune-protected sites, participation of the apoptosis-inducing Fas/FasL molecules could play an im portant role. To assess the possible involvement of the Fas/FasL system in T-cell apoptosis in the PNS of the rat, we characterized Fas and FasL expre ssion on neonatal rat Schwann cells (SC) in vitro. Cells were stimulated in vitro with interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF- alpha), or a combination of both. We observed upregulation of FasL expressi on under the influence of IFN-gamma, while adding TNF-alpha alone to the cu lture medium had no effect. IFN-gamma and TNF-alpha acted synergistically, leading to an increased FasL expression that reached its maximum 70 h after cytokine exposure, as shown by FACS analysis, SDS-PAGE, and Western blot. Fas expression on untreated SC showed fluctuating levels, while addition of IFN-gamma and TNF-alpha suppressed Fas expression completely. These findin gs are in accord with recently published results showing Fas and FasL expre ssion on malignant human cells, derived from brain tumors and upregulation of FasL on astrocytes after exposure to IFN-gamma and TNF-alpha. Furthermor e, FasL-expressing SC could be revealed by immunostaining of sciatic nerve from Lewis rats suffering from experimental autoimmune neuritis (EAN). We s uggest that Fas/FasL expression on SC may contribute to the elimination of invading autoreactive T cells in the PNS in concert with other immune defen se mechanisms. (C) 2000 Wiley-Liss, Inc.