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  • Title: Expression of CD28-related costimulatory molecule and its ligand in inflammatory neuropathies.
    Author: Hu W, Janke A, Ortler S, Hartung HP, Leder C, Kieseier BC, Wiendl H.
    Journal: Neurology; 2007 Jan 23; 68(4):277-82. PubMed ID: 17242332.
    Abstract:
    BACKGROUND: Activation of effector T lymphocytes, mediated in part by costimulatory molecules, is an important mechanism in the pathogenesis of immune-mediated diseases of the peripheral nervous system (PNS). OBJECTIVE: To analyze the expression and distribution pattern of the inducible costimulator (ICOS), a recently identified costimulatory molecule implicated in T-cell activation, and its unique ligand (ICOS-L), in inflammatory disorders of the PNS. METHODS: We studied RNA and protein expression in sural nerve biopsy specimens from patients with Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and vasculitic neuropathy (VN) vs patients with hereditary neuropathies (HNs) serving as a noninflammatory control using reverse-transcriptase PCR and immunohistochemistry. In addition, in vitro analysis was performed by flow cytometry. RESULTS: ICOS and ICOS-L mRNA was found to be significantly upregulated in samples from patients with GBS, CIDP, and VN compared to HNs. Immunohistochemistry identified T lymphocytes as the cellular source of ICOS, whereas macrophages expressed the corresponding ligand ICOS-L. Further analysis revealed that the distribution of ICOS-expressing T cells did not differ between acute and chronic inflamed PNS diseases. Correspondingly, the expression pattern of ICOS-L was similar in the inflamed tissues but differed significantly when compared to HNs. CONCLUSIONS: Inducible costimulator, expressed by T lymphocytes, and inducible costimulator ligand, expressed by macrophages within the peripheral nerve, might not only be relevant in inducing an acute immune response but might also be critically involved in perpetuating inflammation in chronically immune-mediated disorders of the peripheral nervous system.
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