Monocytes stimulated by 110-kDa fibronectin fragments suppress proliferation of anti-CD3-activated T cells.
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.
Birdsall
Holly H
HH
Research Center for AIDS and HIV Infections, Immunology Research Laboratory at the Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX 77030, USA. birdsall@bcm.tmc.edu
Porter
Wendy J
WJ
Trial
JoAnn
J
Rossen
Roger D
RD
D017252:CD3 Complex / Q000276:immunology*; D005353:Fibronectins / Q000494:pharmacology*; D006801:Humans; D007108:Immune Tolerance; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D018950:Lipopolysaccharide Receptors / Q000032:analysis / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects*; D009000:Monocytes / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology*
D017252:CD3 Complex; D005353:Fibronectins; D018950:Lipopolysaccharide Receptors; D010446:Peptide Fragments; C030365:leucine methyl ester; D007930:Leucine