Macrophages suppress T cell responses and arthritis development in mice by producing reactive oxygen species

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Reduced capacity to produce ROS increases the severity of T cell-dependent arthritis in both mice and rats with polymorphisms in neutrophil cytosolic factor 1 (Ncf1) (p47phox). Since T cells cannot exert oxidative burst, we hypothesized that T cell responsiveness is downregulated by ROS produced by APCs. Macrophages have the highest burst capacity among APCs, so to study the effect of macrophage ROS on T cell activation, we developed transgenic mice expressing functional Ncf1 restricted to macrophages. Macrophage-restricted expression of functional Ncf1 restored arthritis resistance to the level of that of wild-type mice in a collagen-induced arthritis model but not in a T cell-independent anti-collagen antibody-induced arthritis model. T cell activation was downregulated and skewed toward Th2 in transgenic mice. In vitro, IL-2 production and T cell proliferation were suppressed by macrophage ROS, irrespective of T cell origin. IFN-gamma production, however, was independent of macrophage ROS but dependent on T cell origin. These effects were antigen dependent but not restricted to collagen type II. In conclusion, macrophage-derived ROS play a role in T cell selection, maturation, and differentiation, and also a suppressive role in T cell activation, and thereby mediate protection against autoimmune diseases like arthritis.


  • Kyra Gelderman
  • Malin Hultqvist
  • Angela Pizzolla
  • Ming Zhao
  • Nandakumar Kutty Selva
  • Ragnar Mattsson
  • Rikard Holmdahl
Enheter & grupper

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Immunologi inom det medicinska området
Sidor (från-till)3020-3028
TidskriftJournal of Clinical Investigation
StatusPublished - 2007
Peer review utfördJa