Anti-CD3 treatment up-regulates programmed cell death protein-1 expression on activated effector T cells and severely impairs their inflammatory capacity
| Autor: | Christopher Paluch, Miyuki Azuma, Margaux Vienne, Anne Cooke, Asha Recino, Jenny M. Phillips, Florence Susan Wong, Maja Wallberg, Herman Waldmann, Duncan Howie |
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| Přispěvatelé: | Cooke, Anne [0000-0003-3327-6081], Apollo - University of Cambridge Repository |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Receptor complex CD3 Complex medicine.medical_treatment CD3 T-Lymphocytes Immunology Cell Programmed Cell Death 1 Receptor Mice SCID Biology Antibodies Green fluorescent protein 03 medical and health sciences transgenic/knockout mouse Mice 0302 clinical medicine Mice Inbred NOD Gene expression medicine Immunology and Allergy Animals Inflammation diabetes Effector tolerance/suppression/anergy Original Articles Molecular biology 3. Good health Cell biology Up-Regulation 030104 developmental biology medicine.anatomical_structure Cytokine biology.protein Original Article Female Antibody Corrigendum 030215 immunology |
| Zdroj: | Immunology |
| ISSN: | 1365-2567 0019-2805 |
| Popis: | Summary T cells play a key role in the pathogenesis of type 1 diabetes, and targeting the CD3 component of the T‐cell receptor complex provides one therapeutic approach. Anti‐CD3 treatment can reverse overt disease in spontaneously diabetic non‐obese diabetic mice, an effect proposed to, at least in part, be caused by a selective depletion of pathogenic cells. We have used a transfer model to further investigate the effects of anti‐CD3 treatment on green fluorescent protein (GFP)+ islet‐specific effector T cells in vivo. The GFP expression allowed us to isolate the known effectors at different time‐points during treatment to assess cell presence in various organs as well as gene expression and cytokine production. We find, in this model, that anti‐CD3 treatment does not preferentially deplete the transferred effector cells, but instead inhibits their metabolic function and their production of interferon‐γ. Programmed cell death protein 1 (PD‐1) expression was up‐regulated on the effector cells from anti‐CD3‐treated mice, and diabetes induced through anti‐PD‐L1 antibody could only be reversed with anti‐CD3 antibody if the anti‐CD3 treatment lasted beyond the point when the anti‐PD‐L1 antibody was washed out of the system. This suggests that PD‐1/PD‐L1 interaction plays an important role in the anti‐CD3 antibody mediated protection. Our data demonstrate an additional mechanism by which anti‐CD3 therapy can reverse diabetogenesis. |
| Databáze: | OpenAIRE |
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