Abstract
Background
Intestinal epithelial cells (IECs) play a pivotal role in controlling immune responses by activation of suppressive CD8+ T regulatory cells (Treg). In Crohn’s disease (CD) this response is impaired due to a defect in CEACAM5 expression on IECs. We previously identified a small region in CEACAM5 able to restore the impaired suppressive activity of CD8+ Treg cells in CD. Here, we tested the functionality of this small peptide in CD patients and evaluated its conformational structure to understand its interaction with T cells.
Methods
Suppression assays were done to assess the ability of peripheral blood (PB) CD8+ T cells isolated from healthy individuals and CD patients and stimulated with the small CEACAM5 peptide to suppress proliferation of activated CD4+ T cells. To understand the role of the Asparagine (N)71 residue present in the CEACAM5 small peptide, which has previously been shown to be pivotal for CD8+ T cell binding to CEACAM5, we tested a library of overlapping peptides in the same region as the small CEACAM5 peptide. Cytokine assays were performed to characterise CEACAM5 peptide-activated CD8+ T cells.
Results
CEACAM5 small peptide activated PB CD8+ T cells from CD patients significantly suppressed CD4+ T-cell proliferation. A new small peptide from the overlapping peptide library containing N71 induced the strongest suppression of proliferation. Peripheral CD8+ T cells produced increased interleukin (IL)-10 upon stimulation with the CEACAM5 peptide.
Conclusion
Our study offers a new approach for modulating the inflammatory state in CD by enhancing the suppressive function of CD8+ T cells using a CEACAM5 small peptide.
DOP66 A CEACAM5 small peptide restores the suppressive activity of CD8 + T cells in patients with Crohn’s disease