DOP66 A CEACAM5 small peptide restores the suppressive activity of CD8 + T cells in patients with Crohn’s disease
G. Roda PhD1, D. Dunkin2, C. Correale1, S. Vetrano1, F. Merlino3, L. Marinelli3, E. Novellino3, L. Mayer4, G. Yeretssian5,6, S. Danese1
1Humanitas Research Hospital, IBD Center, Milano, Italy, 2Icahn School of Medicine at Mount Sinai, Division of Pediatric Gastroenterology and The Mindich Child Health and Development Institute, New York, USA, 3Department of Pharmacy, University of Naple, Naple, Italy, 4Clinical Immunology, Icahn School of Medicine at Mount Sinai, New York, USA, 5The Leona M. and Harry B. Helmsley Charitable Trus, The Leona M. and Harry B. Helmsley Charitable Trust, New York, USA, 6Icahn School of Medicine at Mount Sinai, The Precision Immunology Institute, New York, USA
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.
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.
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.
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.