Regulatory T cells control epitope spreading in autoimmune arthritis independent of cytotoxic T-lymphocyte antigen-4.
Immunology
; 155(4): 446-457, 2018 12.
Article
en En
| MEDLINE
| ID: mdl-29992549
ABSTRACT
CD4+ Foxp3+ regulatory T (Treg) cells can control both cellular and humoral immune responses; however, when and how Treg cells play a predominant role in regulating autoimmune disease remains elusive. To deplete Treg cells in vivo at given time-points, we used a mouse strain, susceptible to glucose-6-phosphate isomerase peptide-induced arthritis (GIA), in which the deletion of Treg cells can be controlled by diphtheria toxin treatment. By depleting Treg cells in the GIA mouse model, we found that a temporary lack of Treg cells at both priming and onset exaggerated disease development. Ablation of Treg cells led to the expansion of antigen-specific CD4+ T cells including granulocyte-macrophage colony-stimulating factor, interferon-γ and interleukin-17-producing T cells, and promoted both T-cell and B-cell epitope spreading, which perpetuated arthritis. Interestingly, specific depletion of cytotoxic T-lymphocyte antigen-4 (CTLA-4) on Treg cells only, was sufficient to protect mice from GIA, due to the expansion of CTLA-4- Treg cells expressing alternative suppressive molecules. Collectively, our findings suggest that Treg cells, independently of CTLA-4, act as the key driving force in controlling autoimmune arthritis development.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Artritis Experimental
/
Enfermedades Autoinmunes
/
Linfocitos T Reguladores
/
Epítopos de Linfocito T
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Antígeno CTLA-4
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Immunology
Año:
2018
Tipo del documento:
Article
País de afiliación:
Suecia