Rheumatoid arthritisben (RA) szenvedő betegek T limfocitáinak NO termelése jelentősen fokozott (közel háromszorosa) egészséges kontrollok T limfocitáihoz képest. RA-ben szenvedő betegek T limfocitáinak citoplazmatikus Ca2+ szintje szintén magasabb kontrollokénál(p 2.5 times more NO than healthy donor T cells (p<0.001). 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). We have shown that the TNF induced NF-?B activation can be inhibited by NO (p<0.001), further suggesting that NO modulates the effects of TNF on T cells. Prolonged exposure to tumor necrosis factor alpha (TNF) downregulates TCR ? in human T cells (p<0.001). By contrast, total and cell surface CD3 ? protein expression is not regulated by TNF. NO pretreatment profoundly inhibits TNF induced TCR ? downregulation in human T cells (p<0.001). TNF increases the expression of src-like adaptor protein (SLAP; a regulator of CD3? expression) in lymphocytes. In addition to its direct effects on T lymphocyte function, histamine regulates cytokine production and T cell signal transduction through regulating NO production. Together, these data indicate that markedly increased NO production of T lymphocytes may contribute to perturbations of immune homeostasis in RA
