Tolerogenic dendritic cells pulsed with islet antigen induce long-term reduction in T-cell autoreactivity in type 1 diabetes patients.
Front Immunol
; 13: 1054968, 2022.
Article
em En
| MEDLINE
| ID: mdl-36505460
ABSTRACT
Introduction:
Restoration of immune tolerance may halt progression of autoimmune diseases. Tolerogenic dendritic cells (tolDC) inhibit antigen-specific proinflammatory T-cells, generate antigen-specific regulatory T-cells and promote IL-10 production in-vitro, providing an appealing immunotherapy to intervene in autoimmune disease progression.Methods:
A placebo-controlled, dose escalation phase 1 clinical trial in nine adult patients with long-standing type 1 diabetes (T1D) demonstrated the safety and feasibility of two (prime-boost) vaccinations with tolDC pulsed with a proinsulin peptide. Immunoregulatory effects were monitored by antigen-specific T-cell assays and flow and mass cytometry.Results:
The tolDC vaccine induced a profound and durable decline in pre-existing autoimmune responses to the vaccine peptide up to 3 years after therapy and temporary decline in CD4 and CD8+ T-cell responses to other islet autoantigens. While major leukocyte subsets remained stable, ICOS+CCR4+TIGIT+ Tregs and CD103+ tissue-resident and CCR6+ effector memory CD4+ T-cells increased in response to the first tolDC injection, the latter declining thereafter below baseline levels.Discussion:
Our data identify immune correlates of mechanistic efficacy of intradermally injected tolDC reducing proinsulin autoimmunity in T1D.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças Autoimunes
/
Diabetes Mellitus Tipo 1
Tipo de estudo:
Clinical_trials
Limite:
Adult
/
Humans
Idioma:
En
Revista:
Front Immunol
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Holanda