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.
Objective Obliterative microvascular lesions are found in the synovial tissue of ~50% of patients with post‐antibiotic Lyme arthritis (LA) and correlate with autoantibodies to certain vascular antigens. In this study, we identified lymphocytes with cytotoxic potential that may also mediate this feature of synovial pathology. Methods The cytotoxic potential of lymphocytes and their T cell receptor (TCR) Vβ gene usage were determined using samples of peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) from patients with antibiotic‐responsive or post‐antibiotic LA. Cell phenotypes were analyzed using flow cytometry and intracellular cytokine staining. Immunohistochemistry was performed on post‐antibiotic synovial tissue samples. Results In SFMC and PBMC samples, the percentages of CD8+ T cells and double‐negative T cells (primarily γδ T cells) were greater among 22 patients with post‐antibiotic LA than in 14 patients with antibiotic‐responsive LA. Moreover, CD8+ T cells and γδ T cells often expressed cytotoxic mediators, granzyme A/granzyme B, and perforin. The same 3 TCR Vβ segments were over‐represented in both CD4+ T cells and CD8+ T cells in SFMC samples from post‐antibiotic LA patients. In synovial tissue samples from 3 patients with post‐antibiotic LA, CD8+ T cells intermixed with CD4+ T cells were seen around blood vessels, and 2 patients with microvascular damage had autoantibodies to vascular‐associated antigens. One of these 2 patients, the one in whom cytotoxicity appeared to be active, had complement (C5b–9) deposition on obliterated vessels. Very few natural killer cells or γδ T cells were seen. Conclusion We propose that CD8+ T cell–mediated cytotoxicity, CD4+ T cell help, autoantibodies to vascular antigens, and complement deposition may each have a role in microvasculature damage in post‐antibiotic LA.
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