Autoreactive T effector memory differentiation mirrors ß cell function in type 1 diabetes.
J Clin Invest
; 128(8): 3460-3474, 2018 08 01.
Article
em En
| MEDLINE
| ID: mdl-29851415
ABSTRACT
In type 1 diabetes, cytotoxic CD8+ T cells with specificity for ß cell autoantigens are found in the pancreatic islets, where they are implicated in the destruction of insulin-secreting ß cells. In contrast, the disease relevance of ß cell-reactive CD8+ T cells that are detectable in the circulation, and their relationship to ß cell function, are not known. Here, we tracked multiple, circulating ß cell-reactive CD8+ T cell subsets and measured ß cell function longitudinally for 2 years, starting immediately after diagnosis of type 1 diabetes. We found that change in ß cell-specific effector memory CD8+ T cells expressing CD57 was positively correlated with C-peptide change in subjects below 12 years of age. Autoreactive CD57+ effector memory CD8+ T cells bore the signature of enhanced effector function (higher expression of granzyme B, killer-specific protein of 37 kDa, and CD16, and reduced expression of CD28) compared with their CD57- counterparts, and network association modeling indicated that the dynamics of ß cell-reactive CD57+ effector memory CD8+ T cell subsets were strongly linked. Thus, coordinated changes in circulating ß cell-specific CD8+ T cells within the CD57+ effector memory subset calibrate to functional insulin reserve in type 1 diabetes, providing a tool for immune monitoring and a mechanism-based target for immunotherapy.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T CD8-Positivos
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Diabetes Mellitus Tipo 1
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Células Secretoras de Insulina
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Memória Imunológica
Tipo de estudo:
Clinical_trials
Limite:
Adult
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Child
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Female
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Humans
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Male
Idioma:
En
Revista:
J Clin Invest
Ano de publicação:
2018
Tipo de documento:
Article