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TNF downmodulates the function of human CD4 + CD25 hi T-regulatory cells

Blood, ISSN: 0006-4971, Vol: 108, Issue: 1, Page: 253-261
2006
  • 701
    Citations
  • 0
    Usage
  • 306
    Captures
  • 0
    Mentions
  • 0
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    701
  • Captures
    306

Article Description

CD4 + CD25 + T-regulatory cells (Tregs) play an essential role in maintaining immunologic homeostasis and preventing autoimmunity. However, little is known about the exogenous factors that regulate their differentiation and function. Here, we report that TNF inhibits the suppressive function of both naturally occurring CD4 + CD25 + Tregs and TGFβ1-induced CD4 + CD25 + T-regulatory cells. The mechanism of this inhibition involves signaling through TNFRII that is constitutively expressed selectively on unstimulated Tregs and that is up-regulated by TNF. TNF-mediated inhibition of suppressive function is related to a decrease in FoxP3 mRNA and protein expression by the Tregs. Notably, CD4 + CD25 hi Tregs isolated from patients with active rheumatoid arthritis (RA) expressed reduced levels of FoxP3 mRNA and protein and poorly suppressed the proliferation and cytokine secretion of CD4 + effector T cells in vitro. Treatment with anti-TNF antibody (infliximab) increased FOXP3 mRNA and protein expression by CD4 + CD25 hi Tregs and restored their suppressive function. Thus, TNF has a novel action in modulating autoimmunity, by inhibiting CD4 + CD25 + Treg activity. (Blood. 2006;108:253-261)

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