Expression of accessory molecules for T-cell activation in peripheral nerve of patients with CIDP and vasculitic neuropathy

Abstract

Vasculitic neuropathy and chronic inflammatory demyelinating polyneuropathy (CIDP) are neuropathies characterized by a T-lymphocyte infiltrate in the peripheral nerves. The microenvironment in which these T cells become activated, and the molecules and cells that play a role in this process are incompletely understood. Using immunohistochemical analysis, we studied the effect of the presence of adhesion, costimulatory and antigen-presenting molecules on different cell types as a precondition for local T-cell activation in human sural nerve biopsies of seven patients with CIDP, three patients with vasculitic neuropathy and three healthy controls. In biopsies from CIDP and vasculitic neuropathy patients, but not in those from healthy controls, Schwann cells expressed the adhesion/T-cell stimulatory molecule CD58 (LFA-3). The CD58 molecule was also present on endothelial cells of all vasculitic neuropathy patients and one CIDP patient. In biopsies from normal controls and patients, CD54 (ICAM-1) expression was detectable on microvascular endothelial cells. In addition, expression of the costimulatory molecule CD86 was detected on vascular tissue in patients with vasculitic neuropathy. Although macrophages were always present in all subjects, expression of the major histocompatibility complex (MHC)-like molecule CD1a by macrophages was restricted to biopsies from two CIDP patients and one vasculitic neuropathy patient. Unexpectedly, Schwann cells of a single vasculitis patient strongly expressed CD1b, a molecule involved in the presentation of self-glycolipids to T cells. Schwann cells in biopsies from patients and normal controls expressed high levels of the invariant chain, CD74, a molecule involved in the intracellular sorting of MHC class II molecules. There was no evidence for the presence of dendritic cells in sural nerve biopsies. These findings support a model in which T-cell activation can be initiated and/or perpetuated locally in sural nerve biopsies of patients with CIDP and vasculitic neuropathy, and predict an important role for Schwann cells and endothelial cells.

Expression of CD1d Molecules by Human Schwann Cells and Potential Interactions with Immunoregulatory Invariant NK T Cells

“…The expression of costimulatory proteins on Schwann cells is currently controversial. Whereas one group reported the presence of CD80 molecules on cultured primary Schwann cells (13), another study failed to detect CD80 and CD86 proteins in normal nerve tissue (9). Under the culture conditions used in the current study, we were unable to detect expression of CD80 on primary Schwann cells (data not shown).…”

“…In general, expression of CD1d proteins on Schwann cells was weak, and its clear demonstration required the use of staining procedures involving several steps of amplification. This observation may explain the failure to detect CD1d on nerve sections in a previous study (9). Nonetheless, the level of CD1d expression on Schwann cells was comparable to that expressed on monocyte-derived DCs, which are known to be potent iNKT activators in cell culture assays.…”

The nonsystemic vasculitic neuropathies

“…Given the dearth of data on NSVN, the group reviewed studies that enrolled patients with SVN or NSVN. Eighteen articles were selected, six class II and twelve class III (all case-control studies, except one retrospective cohort survey) 14,34,54,60,[94][95][96][97][98][99][100][101][102][103][104][105][106][107] , which were analysed to identify variables associated with vasculitic neuropathy. By combining evidence from this review with that from class IV studies that showed active axonal degeneration to be increased in all vasculitic neuropathy series, the guideline group designed consensus diagnostic criteria for histopathologically probable vasculitic neuropathy.…”

Beyond Neurons: Evidence That Immune and Glial Cells Contribute to Pathological Pain States

“…As demyelination and cell death ensue, immune complexes and complement products may be deposited in VN nerves (51,105), leading to more efficient clearing of the debris by activated macrophages. Whether there is an increase in T lymphocytes relative to normal controls is controversial (24,321). If present, T cells may have been attracted to the region primarily as the result of the underlying vasculitis and appear to be infiltrating into the nerve due to ischemic-induced blood-nerve barrier breakdown.…”