Abstract
Objective
Deficiency of decay‐accelerating factor 1 (termed Daf1 in mice) has been shown to exacerbate autoimmunity, and recent studies have suggested that this may be explained by Daf1 acting as a regulator of T cell immunity. The aim of this study was to determine whether Daf1 expression on T cells is modulated during development of autoimmunity in mice.
Methods
To test this hypothesis, we examined Daf1 levels in NZB, DBA/2, and B10.S mice before and after induction of murine mercury‐induced autoimmunity (mHgIA). Daf1 was measured by real‐time polymerase chain reaction and flow cytometry, and levels of Daf1 were correlated with markers of lymphocyte activation and cytokine production.
Results
Autoimmune‐prone NZB mice had low endogenous levels of Daf1 irrespective of the induction of mHgIA. Induction of autoimmunity reduced Daf1 expression in mHgIA‐sensitive B10.S mice, particularly on activated/memory (CD44^high^) CD4+ T cells that accumulate as a result of exposure to mercury. Murine mercury‐induced autoimmunity–resistant DBA/2 mice, which fail to accumulate CD44^high^ T cells, showed no change in Daf1 expression. Modulation of Daf1 expression was found to require CD4+ T cell costimulation, since B10.S mice deficient in CD28 were unable to down‐regulate Daf1 or accumulate activated/memory CD4+ T cells. In B10.S mice exposed to mercury, the production of interleukin‐4 (IL‐4), but not that of IL‐2 or interferon‐γ, in the spleen was associated with CD44^high^,Daf1^low^,CD4+ T cells.
Conclusion
These findings demonstrate that reduction of Daf1 expression is closely associated with CD4+ T cell activation and the accumulation of CD44^high^(activated/memory),CD4+ T cells in both spontaneous and induced systemic autoimmune disease.