Basic—Alimentary TractAnti–Tumor Necrosis Factor-α Antibodies Induce Regulatory Macrophages in an Fc Region-Dependent Manner
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Antibodies and Reagents
Infliximab, certolizumab, adalimumab, and etanercept were prepared according to the manufacturers' recommendations. Certolizumab-IgG was obtained from UCB (UCB, Brussels, Belgium), and IgG1k was obtained from Sigma (St. Louis, Missouri).
Cell Isolation and Culture
Peripheral blood mononuclear cells (PBMCs) from healthy volunteers were isolated by Ficoll Paque density-gradient centrifugation. After washing, monocytes were isolated by Percoll density-gradient centrifugation. CD3-positive T cells were isolated from PBMCs
Anti-TNFα Compounds Bind mTNFα on Activated T Cells to Varying Degrees
To assess binding of compounds to mTNFα, anti-TNFα compounds and IgG control were labeled with a fluorescent dye, and binding of fluorescent-labeled compounds to activated T cells was compared with binding to nonactivated cells. Binding of infliximab and adalimumab to mTNFα was highly efficient, binding of certolizumab was intermediate, and binding of etanercept was low compared with the IgG control (Figure 1).
Anti-TNFα Compounds With an Fc Region Suppress T-Cell Activation but Only in an MLR
We examined the effect of various anti-TNFα compounds on the proliferation of
Discussion
In the present study, we found that drugs used to target TNFα have different functional properties. The anti-TNFα antibodies bind to mTNFα on activated T cells and inhibit their proliferation but only in the presence of APCs. In contrast, a soluble TNFα receptor or F(ab')2 fragments of the anti-TNFα antibodies do not affect T-cell proliferation under the same circumstances. Our experiments show that the immunosuppressive properties of the anti-TNFα antibodies are dependent on their Fc region.
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Conflicts of interest These authors disclose the following: Gijs van den Brink receives grants/research support from MSD, Ferring, and Giuliani; Daniel Hommes receives grants/research support and is a consultant for Abbott, MSD, UCB, Giuliani, Ferring, Serono, AstraZeneca, Falk, and Tramedico. The remaining authors disclose no conflicts.
Funding This study was financially supported by UCB.