Regulatory T Cells as Immunotherapy

Abstract

Regulatory T cells (Tregs) suppress exuberant immune system activation and promote immunologic tolerance. Because Tregs modulate both innate and adaptive immunity, the biomedical community has developed an intense interest in using Tregs for immunotherapy. Conditions that require clinical tolerance to improve outcomes – autoimmune disease, solid organ transplantation, and hematopoietic stem cell transplantation – may benefit from Treg immunotherapy. Investigators have designed ex vivo strategies to isolate, preserve, expand, and infuse Tregs. Protocols to manipulate Treg populations in vivo have also been considered. Barriers to clinically feasible Treg immunotherapy include Treg stability, off-cell effects, and demonstration of cell preparation purity and potency. Clinical trials involving Treg adoptive transfer to treat graft versus host disease preliminarily demonstrated the safety and efficacy of Treg immunotherapy in humans. Future work will need to confirm the safety of Treg immunotherapy and establish the efficacy of specific Treg subsets for the treatment of immune-mediated disease.

Engagement of SLAMF3 enhances CD4 + T-cell sensitivity to IL-2 and favors regulatory T-cell polarization in systemic lupus erythematosus

“…SLAMF3 stimulation could be beneficial in patients who exhibit resistance to IL-2 therapy or who cannot tolerate recombinant IL-2 treatment. Similarly, engagement of SLAMF3 could offer significant adjuvant therapeutic value to clinical trials in which in vitro expanded Tregs are transfused to patients with SLE, diabetes, and GVHD (44).…”

Discarded Human Thymus Is a Novel Source of Stable and Long-Lived Therapeutic Regulatory T Cells

“…The knowledge that Tregs can suppress immune responses against autoantigens and alloantigens has prompted exploration of Tregbased tolerogenic therapies for treatment of autoimmune disorders, organ transplant rejection, and graft-versus-host disease (GVHD) (4)(5)(6). Indeed, animal model studies have shown that adoptive Treg transfer is an effective strategy for suppressing immune-mediated diseases and immunologic complications of transplantation (7)(8)(9)(10).…”

Yin-yang regulating effects of cancer-associated genes, proteins, and cells: An ancient Chinese concept in vogue in modern cancer research

“…Subpopulations of regulatory T cells (Tregs), which promote or inhibit the immune response, display yin-yang characteristics under certain conditions (35). The depletion of Tregs leads to the lack of suppression of immune cells, causing an excessive immune response and autoimmunity and promoting anti-tumor responses, while the expansion of Tregs can counteract autoimmunity and inhibit anti-tumor responses (36).…”