Suppression of Human Dendritic Cells by Regulatory T Cells.

Regulatory T cells (Tregs) suppress immune responses via a variety of mechanisms and can be used as a cellular therapy to induce tolerance. The function of Tregs is commonly assessed in vitro using assays that measure suppression of effector T cell proliferation and/or cytokine production. However, Tregs can also suppress the function of antigen presenting cells, creating a need for methodology to routinely measure this aspect of their function.

Functional effects of chimeric antigen receptor co-receptor signaling domains in human regulatory T cells.

Antigen-specific regulatory T cells (T) engineered with chimeric antigen receptors (CARs) are a potent immunosuppressive cellular therapy in multiple disease models and could overcome shortcomings of polyclonal T therapy. CAR therapy was initially developed with conventional T cells, which have different signaling requirements than do T To date, most of the CAR T studies used second-generation CARs, encoding a CD28 or 4-1BB co-receptor signaling domain and CD3ζ, but it was not known if this CAR design was optimal for T Using a human leukocyte antigen-A2-specific CAR platform and human T, we compared 10 CARs with different co-receptor signaling domains and systematically tested their function and CAR-stimulated gene expression profile. T expressing a CAR encoding CD28wt were markedly superior to all other CARs tested in an in vivo model of graft-versus-host disease.

An optimized method to measure human FOXP3 regulatory T cells from multiple tissue types using mass cytometry.

We optimized a method to detect FOXP3 by mass cytometry and compared the resulting data to conventional flow cytometry. We also demonstrated the utility of the protocol to profile antigen-specific Tregs from whole blood, or Tregs from tissues such as cord blood, thymus and synovial fluid.

Engineered Tolerance: Tailoring Development, Function, and Antigen-Specificity of Regulatory T Cells.

Regulatory T cells (Tregs) are potent suppressors of immune responses and are currently being clinically tested for their potential to stop or control undesired immune responses in autoimmunity, hematopoietic stem cell transplantation, and solid organ transplantation. Current clinical approaches aim to boost Tregs either by using Treg-promoting small molecules/proteins and/or by adoptive transfer of expanded Tregs. However, the applicability of Treg-based immunotherapies continues to be hindered by technical limitations related to cell isolation and expansion of a pure, well-characterized, and targeted Treg product.

Antigen-specific regulatory T cells: are police CARs the answer?

Cellular therapy with T-regulatory cells (Tregs) is a promising strategy to control immune responses and restore immune tolerance in a variety of immune-mediated diseases, such as transplant rejection and autoimmunity. Multiple clinical trials are currently testing this approach, typically by infusing a single dose of polyclonal Tregs that have been expanded in vitro. However, evidence from animal models of Treg therapy has clearly shown that antigen-specific Tregs are vastly superior to polyclonal cells, meaning that fewer cells are needed for the desired therapeutic effect.

Regulatory T cells produce profibrotic cytokines in the skin of patients with systemic sclerosis.

Background: Systemic sclerosis (SSc) is an autoimmune disorder characterized by fibrosis of the skin and internal organs. Pathologic conversion of regulatory T (Treg) cells into inflammatory cytokine-producing cells is thought to be an important step in the progression of autoimmunity, but whether loss of normal Treg cell function contributes to SSc is unknown.

Objective: We sought to determine whether Treg cells in the blood and skin of patients with SSc acquired abnormal production of effector cytokines.