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: | 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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