Changes in T-cell subsets identify responders to FcR-nonbinding anti-CD3 mAb (teplizumab) in patients with type 1 diabetes.
Eur J Immunol
; 46(1): 230-41, 2016 Jan.
Article
en En
| MEDLINE
| ID: mdl-26518356
ABSTRACT
The mechanisms whereby immune therapies affect progression of type 1 diabetes (T1D) are not well understood. Teplizumab, an FcR nonbinding anti-CD3 mAb, has shown efficacy in multiple randomized clinical trials. We previously reported an increase in the frequency of circulating CD8(+) central memory (CD8CM) T cells in clinical responders, but the generalizability of this finding and the molecular effects of teplizumab on these T cells have not been evaluated. We analyzed data from two randomized clinical studies of teplizumab in patients with new- and recent-onset T1D. At the conclusion of therapy, clinical responders showed a significant reduction in circulating CD4(+) effector memory T cells. Afterward, there was an increase in the frequency and absolute number of CD8CM T cells. In vitro, teplizumab expanded CD8CM T cells by proliferation and conversion of non-CM T cells. Nanostring analysis of gene expression of CD8CM T cells from responders and nonresponders versus placebo-treated control subjects identified decreases in expression of genes associated with immune activation and increases in expression of genes associated with T-cell differentiation and regulation. We conclude that CD8CM T cells with decreased activation and regulatory gene expression are associated with clinical responses to teplizumab in patients with T1D.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Subgrupos de Linfocitos T
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Linfocitos T CD8-positivos
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Diabetes Mellitus Tipo 1
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Anticuerpos Monoclonales Humanizados
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Transcriptoma
Tipo de estudio:
Clinical_trials
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Prognostic_studies
Límite:
Adolescent
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Adult
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Child
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Female
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Humans
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Male
Idioma:
En
Revista:
Eur J Immunol
Año:
2016
Tipo del documento:
Article
País de afiliación:
Estados Unidos