CD4 T-cell autoreactivity to the mitochondrial autoantigen PDC-E2 in AMA-negative primary biliary cirrhosis

Shinji Shimoda, Hiroshi Miyakawa, Minoru Nakamura, Hiromi Ishibashi, Kentaro Kikuchi, Hiroto Kita, Hiroaki Niiro, Youjirou Arinobu, Nobuyuki Ono, Ian R. Mackay, M. Eric Gershwin, Koichi Akashi

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

Approximately 5% of patients with primary biliary cirrhosis (PBC) lack characteristic anti-mitochondrial antibodies (AMA). Yet clinically AMA+ and AMA- patients are similar. Using both AMA+ and AMA- patients, we quantitated the frequency of autoreactive T cells that respond to the major CD4 T-cell epitope, PDC-E2 163-176, using limiting dilution assays and quantitation of IFN-γ, IL-10 and IL-4. Further, based on data that both PBC patients and healthy subjects have CD4+ T cells that recognize PDC-E2 163-176 but with differing costimulation requirements, assays were performed using two different antigen-presenting cell (APC) systems: either autologous peripheral blood mononuclear cells (PBMC) or HLA DR53 transfected mouse fibroblast cell lines (L-DR53). When costimulation-incompetent L-DR53 were used as APCs, the PDC-E2 CD4 T-cell frequency and capacity for IFN-γ production were equivalent in both AMA+ and AMA- patients but the frequencies of such cells were significantly lower in normals, with IL-10 production similar in all three groups. Thus, in PBC there is 'universal' autoreactive CD4+ T-cell immune responsiveness to the critical autoantigen, PDC-E2. These observations emphasize that the mitochondrial autoreactivity in PBC is a multi-lineage response and hence, AMA-negative PBC may be an anachronism that refers only to sera autoantibodies.

Original languageEnglish (US)
Pages (from-to)110-115
Number of pages6
JournalJournal of Autoimmunity
Volume31
Issue number2
DOIs
StatePublished - Sep 2008

Keywords

  • Cell proliferation
  • Primary biliary cirrhosis
  • Seronegative
  • T cells

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Fingerprint Dive into the research topics of 'CD4 T-cell autoreactivity to the mitochondrial autoantigen PDC-E2 in AMA-negative primary biliary cirrhosis'. Together they form a unique fingerprint.

  • Cite this

    Shimoda, S., Miyakawa, H., Nakamura, M., Ishibashi, H., Kikuchi, K., Kita, H., Niiro, H., Arinobu, Y., Ono, N., Mackay, I. R., Gershwin, M. E., & Akashi, K. (2008). CD4 T-cell autoreactivity to the mitochondrial autoantigen PDC-E2 in AMA-negative primary biliary cirrhosis. Journal of Autoimmunity, 31(2), 110-115. https://doi.org/10.1016/j.jaut.2008.05.003