Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Anti-CD3 treatment up-regulates programmed cell death protein-1 expression on activated effector T cells and severely impairs their inflammatory capacity

Wallberg, Maja, Recino, Asha, Phillips, Jenny, Howie, Duncan, Vienne, Margaux, Paluch, Christopher, Azuma, Miyuki, Wong, Florence Susan, Waldmann, Herman and Cooke, Anne 2017. Anti-CD3 treatment up-regulates programmed cell death protein-1 expression on activated effector T cells and severely impairs their inflammatory capacity. Immunology 151 (2) , pp. 248-260. 10.1111/imm.12729

[img]
Preview
PDF - Published Version
Available under License Creative Commons Attribution Non-commercial.

Download (1MB) | Preview

Abstract

T cells play a key role in the pathogenesis of type 1 diabetes, and target-ing the CD3 component of the T-cell receptor complex provides one ther-apeutic approach. Anti-CD3 treatment can reverse overt disease inspontane ously diabetic non-obese diabetic mice, an effect proposed to, atleast in part, be caused by a selective depleti on of pathogenic cells. Wehave used a transfer model to further investigate the effects of anti-CD3treatment on green fluorescent protein (GFP)+islet-specific effecto r Tcells in vivo. The GFP expression allowed us to isolate the known effectorsat different time-points during treatment to assess cell presence in variousorgans as well as gene expression and cytokine production. We find, inthis model, that anti-CD3 treatment does not preferentially deplete thetransferred effector cells, but instead inhibits their metabolic function andtheir production of interferon-c. Programmed cell death protein 1 (PD-1)expression was up-regulated on the effector cells from anti-CD3-treatedmice, and diabetes induced through anti-PD-L1 antibod y could only bereversed with anti-CD3 antibody if the anti-CD3 treatment lasted beyondthe point when the anti-PD-L1 antibody was washed out of the system.This suggests that PD-1/PD-L1 interac tion plays an important role in theanti-CD3 antibody mediated protection. Our data demonstrate an addi-tional mechanism by which anti-CD3 therapy can reverse diabetogenesis.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Wiley
ISSN: 0019-2805
Date of First Compliant Deposit: 18 August 2017
Date of Acceptance: 13 February 2017
Last Modified: 18 Aug 2017 15:42
URI: http://orca.cf.ac.uk/id/eprint/102219

Citation Data

Cited 7 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics