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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.

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Benaroya Research Institute at Virginia Mason, Seattle, WA, USA.
Departments of Immunobiology and Internal Medicine, Yale University, New Haven, CT, USA.
Immune Tolerance Network, San Francisco, CA, USA.
Immune Tolerance Network, Bethesda, MD, USA.
Benaroya Research Institute at Virginia Mason, Seattle, WA, USA; Immune Tolerance Network, Bethesda, MD, USA.
Immune Tolerance Network, Bethesda, MD, USA. Electronic address:


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.


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

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