Remodeling T cell compartments during anti-CD3 immunotherapy of type 1 diabetes.
Cell Immunol
; 319: 3-9, 2017 Sep.
Article
em En
| MEDLINE
| ID: mdl-28844471
ABSTRACT
The immunological mechanism(s) of action whereby teplizumab preserves C-peptide levels in the progression of patients with recent onset type 1 diabetes (T1D) is still not well understood. In the present study, we evaluated the kinetics of T cell modulation in peripheral blood following two 14-day courses of teplizumab therapy one year apart in recent onset T1D participants in the AbATE clinical trial. Transient rises in PD-1+Foxp3+ Treg and potentially anergic (CD57-KLRG1-PD-1+) cells in the circulating CD4 T cell compartment were paralleled by more profound increases in circulating CD8 T cells with traits of exhaustion (CD57-KLRG1+PD-1+, TIGIT+KLRG1+, and persistent down-modulation of CD127). The observed phenotypic changes across cell types were associated with favorable response to treatment in the subgroup of study participants that did not develop anti-drug antibodies after the first course of therapy. These findings provide new insights on the duration and complexity of T cell modulation with teplizumab therapy in recent onset T1D, and in addition, suggest that coordinated immune mechanisms of tolerance that favor CD4 Treg function and restrain CD4 non-Treg and CD8 T cell activation may contribute to treatment success.
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Base de dados:
MEDLINE
Assunto principal:
Linfócitos T Reguladores
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Linfócitos T CD8-Positivos
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Diabetes Mellitus Tipo 1
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Anticorpos Monoclonais Humanizados
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Hipoglicemiantes
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Tolerância Imunológica
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article