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TNF{alpha} blockade impairs dendritic cell survival and function in rheumatoid arthritis [Extended Report]
Annals of Rheumatic Diseases, 10/07/09

Baldwin HM et al. – Our data show that TNF &alpha blockade has profound effects on DC function with downstream, potentially immunoregulatory, effects on T-cells. These data provide an interesting new insight into the potential mechanism by which anti-TNF drugs contribute to the restoration of immunoregulation in RA patients

Methods

Two complementary approaches were taken
In the first 'in vitro' approach monocyte-derived DC from healthy donors were matured with LPS and treated with TNF &alpha antagonists in vitro for 48 hours
In the second 'ex vivo' approach monocyte-derived DC were generated from RA patients before and 8-12 weeks into anti-TNF &alpha treatment
DC were analysed for survival, phenotype, cytokine production and T cell stimulatory capacity

Results

TNF &alpha blockade during DC maturation in vitro induced approximately 40 % of DC to undergo apoptosis.
Importantly, the surviving DC displayed semi-mature phenotype with reduced levels of HLA-DR, CD80, CD83, CD86 and CCR7, and their production of IL-10 enhanced as compared to DC matured without TNFnantagonists
Anti-TNF-treated DC were poor stimulators of T cell proliferation and polarised T-cell development towards higher IL-10/lower IFN- cytokine profile
DC derived from RA patients after anti-TNF &alpha treatment showed impaired upregulation of CD80 and CD86 upon LPS activation and displayed poor T cell stimulatory activity

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