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 ORCID: https://orcid.org/0000-0002-2812-8845, 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

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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:	05 May 2023 21:22
URI:	https://orca.cardiff.ac.uk/id/eprint/102219

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