Nitric oxide production of T lymphocytes is increased in rheumatoid arthritis.
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 Ca(2+) 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.
Nagy
György
G
Department of Rheumatology, Semmelweis University, Medical School, Budapest, Hungary. gyorgyngy@gmail.com
Clark
Joanna M
JM
Buzas
Edit
E
Gorman
Claire
C
Pasztoi
Maria
M
Koncz
Agnes
A
Falus
Andras
A
Cope
Andrew P
AP
D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D009569:Nitric Oxide / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000378:metabolism*
D009569:Nitric Oxide; D002118:Calcium