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Cell Immunol. 2017 Sep;319:3-9. doi: 10.1016/j.cellimm.2017.07.007. Epub 2017 Aug 18.

Remodeling T cell compartments during anti-CD3 immunotherapy of type 1 diabetes.

Author information

1
Benaroya Research Institute at Virginia Mason, Seattle, WA, USA.
2
Departments of Immunobiology and Internal Medicine, Yale University, New Haven, CT, USA.
3
Immune Tolerance Network, San Francisco, CA, USA.
4
Immune Tolerance Network, Bethesda, MD, USA.
5
Benaroya Research Institute at Virginia Mason, Seattle, WA, USA; Immune Tolerance Network, Bethesda, MD, USA.
6
Immune Tolerance Network, Bethesda, MD, USA. Electronic address: kharris@immunetolerance.org.

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.

KEYWORDS:

Anti-CD3 monoclonal antibody; Immune tolerance; Immunotherapy; T cell inactivation; T lymphocyte; Type 1 diabetes

PMID:
28844471
PMCID:
PMC5614459
DOI:
10.1016/j.cellimm.2017.07.007
[Indexed for MEDLINE]
Free PMC Article

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