A Trichosanthin-derived peptide suppresses type 1 immune responses by TLR2-dependent activation of CD8(+)CD28(-) Tregs
Copyright © 2013 Elsevier Inc. All rights reserved.
| Veröffentlicht in: | Clinical immunology (Orlando, Fla.). - 1999. - 153(2014), 2 vom: 15. Aug., Seite 277-87 |
|---|---|
| 1. Verfasser: | |
| Weitere Verfasser: | , , , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2014
|
| Zugriff auf das übergeordnete Werk: | Clinical immunology (Orlando, Fla.) |
| Schlagworte: | Journal Article Research Support, Non-U.S. Gov't CD8(+)CD28(−) Treg EAE TLR2 signaling Trichosanthin-derived peptide CD28 Antigens CD8 Antigens Peptides Tlr2 protein, mouse mehr... |
| Zusammenfassung: | Copyright © 2013 Elsevier Inc. All rights reserved. A group of 15-aa-long Trichosanthin-derived peptides was synthesized and screened based on their differential abilities to induce low-responsiveness in mouse strains with high and low susceptibility. One of them was conjugated to form a homo-tetramer Tk-tPN. At concentrations of 0.1-50 μg/ml, Tk-tPN activated CD8(+)CD28(-) Tregs in vitro to induce immune suppression as effectively as the native Trichosanthin but did not exhibit cytotoxicity. In EAE mice which were pre-treated with Tk-tPN or Tk-tPN-activated CD8(+) T cells, a marked attenuation of clinical scores was recorded together with an expansion of the CD8(+)CD28(-) Treg from 2.2% to 36.1% in vivo. A pull-down assay and signal transduction analyses indicated that the ability of Tk-tPN to convert the CD8(+)CD28(-) Treg-related cytokine secretion pattern from type 1 to type 2 depends on the TLR2-initiated signaling in macrophages. The high production of IL-4/IL-10 by the Tk-tPN-activated CD8(+)CD28(-) Treg suggests the value of using Tk-tPN as a therapeutic reagent for Th1-dominant immunological diseases |
|---|---|
| Beschreibung: | Date Completed 05.09.2014 Date Revised 16.11.2017 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1521-7035 |
| DOI: | 10.1016/j.clim.2014.05.005 |