Monocytes stimulated by 110-kDa fibronectin fragments suppress proliferation of anti-CD3-activated T cells

J Immunol. 2005 Sep 1;175(5):3347-53. doi: 10.4049/jimmunol.175.5.3347.


One hundred ten to 120-kDa fragments of fibronectin (FNf), generated by proteases released in the course of tissue injury and inflammation, stimulate monocytes to produce proinflammatory cytokines, promote mononuclear leukocytes (MNL) transendothelial migration, up-regulate monocyte CD11b and CD86 expression, and induce monocyte-derived dendritic cell differentiation. To investigate whether the proinflammatory consequences of FNf are offset by responses that can suppress proliferation of activated T lymphocytes, we investigated the effect of FNf-treated MNL on autologous T lymphocytes induced to proliferate by substrate-immobilized anti-CD3. FNf-stimulated MNL suppressed anti-CD3-induced T cell proliferation through both contact-dependent and contact-independent mechanisms. Contact-independent suppression was mediated, at least in part, by IL-10 and TGF-beta released by the FNf-stimulated MNL. After 24-48 h exposure to FNf, activated T cells and monocytes formed clusters displaying CD25, CD14, CD3, and CD4 that were not dissociable by chelation of divalent cations. Killing monocytes with l-leucine methyl ester abolished these T cell-monocyte clusters and the ability of the FNf-stimulated MNL to suppress anti-CD3 induced T cell proliferation. Thus, in addition to activating MNL and causing them to migrate to sites of injury, FNf appears to induce suppressor monocytes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • CD3 Complex / immunology*
  • Fibronectins / pharmacology*
  • Humans
  • Immune Tolerance
  • Leucine / analogs & derivatives
  • Leucine / pharmacology
  • Lipopolysaccharide Receptors / analysis
  • Lipopolysaccharide Receptors / physiology
  • Lymphocyte Activation / drug effects*
  • Monocytes / drug effects
  • Monocytes / physiology*
  • Peptide Fragments / pharmacology*
  • T-Lymphocytes / immunology*


  • CD3 Complex
  • Fibronectins
  • Lipopolysaccharide Receptors
  • Peptide Fragments
  • leucine methyl ester
  • Leucine