Soluble CD137 Ameliorates Acute Type 1 Diabetes by Inducing T Cell Anergy.
Front Immunol
; 10: 2566, 2019.
Article
em En
| MEDLINE
| ID: mdl-31787971
ABSTRACT
We show here that soluble CD137 (sCD137), the alternately spliced gene product of Tnfsfr9, effectively treats acute type 1 diabetes (T1D) in nonobese diabetic (NOD) mice. sCD137 significantly delayed development of end-stage disease, preserved insulin+ islet beta cells, and prevented progression to end-stage T1D in some mice. We demonstrate that sCD137 induces CD4+ T cell anergy, suppressing antigen-specific T cell proliferation and IL-2/IFN-γ secretion. Exogenous IL-2 reversed the sCD137 anergy effect. sCD137 greatly reduces inflammatory cytokine production by CD8 effector memory T cells, critical mediators of beta cell damage. We demonstrate that human T1D patients have decreased serum sCD137 compared to age-matched controls (as do NOD mice compared to NOD congenic mice expressing a protective Tnfsfr9 allele), that human sCD137 is secreted by regulatory T cells (Tregs; as in mice), and that human sCD137 induces T cell suppression in human T cells. These findings provide a rationale for further investigation of sCD137 as a treatment for T1D and other T cell-mediated autoimmune diseases.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T CD4-Positivos
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Anergia Clonal
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Diabetes Mellitus Tipo 1
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Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral
Limite:
Animals
Idioma:
En
Revista:
Front Immunol
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos