CD8+ T-cell immunity in chronic inflammatory demyelinating polyradiculoneuropathy

Chronic inflammatory demyelinating polyradiculopathy (CIDP) is a common, but often misdiagnosed disease of the peripheral nervous system with assumed autoimmune pathogenesis. While current concepts of CIDP postulate a pathogenetic role of B cells and (auto)antibodies, the relevance of CD8 T cells pr...

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Vydáno v:Neurology Ročník 78; číslo 6; s. 402
Hlavní autoři: Schneider-Hohendorf, T, Schwab, N, Uçeyler, N, Göbel, K, Sommer, C, Wiendl, H
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 07.02.2012
Témata:
Adult
Aged
CD8-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - pathology
Humans
Male
Middle Aged
Polyradiculoneuropathy, Chronic Inflammatory Demyelinating - immunology
Polyradiculoneuropathy, Chronic Inflammatory Demyelinating - pathology
Receptors, Antigen, T-Cell - immunology
ISSN:1526-632X, 1526-632X
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Shrnutí:Chronic inflammatory demyelinating polyradiculopathy (CIDP) is a common, but often misdiagnosed disease of the peripheral nervous system with assumed autoimmune pathogenesis. While current concepts of CIDP postulate a pathogenetic role of B cells and (auto)antibodies, the relevance of CD8 T cells present in the biopsies is still elusive. Thus, we asked whether nervous tissue infiltrating and blood-derived lymphocytes in CIDP are clonally expanded to evaluate the involvement of T cells in the pathogenesis of the disease. We characterized the clonal composition of the T-cell receptor repertoire in sural nerve biopsies (n = 25) and matching peripheral blood (n = 12) of patients with CIDP using PCR-based CDR3 spectratyping and subsequent DNA sequencing. As controls we used inflammatory myopathies (dermatomyositis, inclusion body myositis) and nonpathologic control biopsies. Immunohistochemistry was employed to visualize expanded CD8+ T-cell populations in sural nerve biopsies. In contrast to controls, T cells in CIDP biopsies showed strong monoclonal and oligoclonal restrictions in their T-cell receptor repertoire. Strikingly, clonal expansions found in the biopsies were reflected in the CD8+ T-cell pool of patients' peripheral blood. Clones overlapping between blood and biopsy could be confirmed by CDR3 sequencing. Finally, the predominance of expanded nerve-infiltrating CD8+ T-cell clones was visualized by immunohistochemistry. Together, these data provide strong evidence for an antigen-driven, major histocompatibility complex class I restricted, CD8+ T-cell-mediated attack against peripheral nerve tissue components contributing to the pathogenesis of CIDP.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:1526-632X
1526-632X
DOI:10.1212/WNL.0b013e318245d250