Nitric oxide production of T lymphocytes is increased in rheumatoid arthritis

György Nagy, Joanna M. Clark, E. Búzás, Claire Gorman, Maria Pasztoi, A. Koncz, A. Falus, Andrew P. Cope

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Experimental and clinical evidence for T cell involvement in the pathology of rheumatoid arthritis (RA) is compelling, and points to a local dysregulation of T cell function in the inflamed joint. Nitric oxide (NO) has been shown to regulate T cell function under physiological conditions, but overproduction of NO may contribute to lymphocyte dysfunction characteristic of RA. Several investigations in patients with RA have documented evidence of increased NO synthesis, but these studies have focused largely on macrophage-derived NO and its impact on innate immune and inflammatory responses. In this study, we set out to explore the contribution that T cells make to NO production. We find that T cells from RA patients produce >2.5 times more NO than healthy donor T cells (p <0.001). Although NO is an important physiological mediator of mitochondrial biogenesis, mitochondrial mass is similar in RA and control T cells. In contrast, increased NO production is associated with increased cytoplasmic Ca2+ concentrations in RA T cells (p <0.001). In vitro treatment of human peripheral blood lymphocytes, or Jurkat cells with TNF increases NO production (p = 0.006 and p = 0.001, respectively), whilst infliximab treatment in RA patients decreases T cell derived NO production within 6 weeks of the first infusion (p = 0.005). Together, these data indicate that TNF induced NO production in T lymphocytes may contribute to perturbations of immune homeostasis in RA.

Original languageEnglish
Pages (from-to)55-58
Number of pages4
JournalImmunology Letters
Volume118
Issue number1
DOIs
Publication statusPublished - Jun 15 2008

Fingerprint

Rheumatoid Arthritis
Nitric Oxide
T-Lymphocytes
Lymphocytes
Jurkat Cells
Nitric Oxide Donors
Organelle Biogenesis
Innate Immunity
Blood Cells
Homeostasis
Joints
Macrophages
Pathology
Therapeutics

Keywords

  • Mitochondrial biogenesis
  • Nitric oxide
  • Rheumatoid arthritis

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Nitric oxide production of T lymphocytes is increased in rheumatoid arthritis. / Nagy, György; Clark, Joanna M.; Búzás, E.; Gorman, Claire; Pasztoi, Maria; Koncz, A.; Falus, A.; Cope, Andrew P.

In: Immunology Letters, Vol. 118, No. 1, 15.06.2008, p. 55-58.

Research output: Contribution to journalArticle

Nagy, György ; Clark, Joanna M. ; Búzás, E. ; Gorman, Claire ; Pasztoi, Maria ; Koncz, A. ; Falus, A. ; Cope, Andrew P. / Nitric oxide production of T lymphocytes is increased in rheumatoid arthritis. In: Immunology Letters. 2008 ; Vol. 118, No. 1. pp. 55-58.
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