Enhanced B7 costimulatory molecule expression in inflammatory human sural nerve biopsies

Open Access
Publisher Website
Google Scholar
Abstract
OBJECTIVES To define the role of the costimulatory molecules B7–1 and B7–2 in inflammatory disorders of the peripheral nervous system. B7 molecules are essential for effective antigen presentation and may determine the differentiation of T cells into a Th-1 or Th-2 phenotype, thus modulating immune response and disease course. METHODS Forty nine sural nerve biopsies from patients with neuroborreliosis, Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), CIDP variants and hereditary neuropathies, and those with no detectable abnormality were investigated. The expression of B7–1 and B7–2 mRNA and protein was investigated by polymerase chain reaction (PCR) and immunocytochemistry. RESULTS B7–1 mRNA was strongly upregulated in both cases of neuroborreliosis, in two cases of GBS and one case of variant CIDP. Moderate to low levels were detected in the remaining GBS and CIDP biopsies and were rarely found in a non-inflammatory control group consisting of hereditary neuropathy and normal nerves. At the immunocytochemical level, strong expression of B7–1 protein was found in both neuroborreliosis cases, and moderate or low expression in six of eight GBS cases and seven of 17 CIDP cases investigated, whereas only one of five non-inflammatory control nerves showed staining, which was very weak. In neuroborreliosis, B7–1 protein was found very pronounced in epineurial infiltrates, whereas in GBS and CIDP, labelling was predominantly endoneurial and localised to putative macrophages. B7–2 mRNA and protein were expressed only at low levels in neuroborreliosis and selected autoimmune neuropathy cases, and were essentially absent from non-inflammatory controls. CONCLUSIONS B7 molecules are expressed in the peripheral nervous system and regulated during disease, and their presence in macrophages underlines the putative function of endoneurial macrophages as local antigen presenting cells in the immunopathology of peripheral nerve. B7–1 rather than B7–2 is preferentially upregulated, possibly promoting the induction of a Th-1-type T cell response within the nerve.