Interpretation of transplant biopsies and immune responses following Treg cell therapy

Regulatory T cells (Treg) are now well established as vital participants in maintaining self-tolerance and preventing autoimmunity. Tregs have already been shown to be effective in preventing graft-versus-host disease in clinical bone marrow transplantation, and numerous animal studies have suggested a therapeutic role for Treg in solid organ transplantation. Recent advances in Treg isolation and expansion have the field poised to perform trials of therapeutic Treg infusion in solid organ transplantation worldwide. An important component of these trials will be the detection of infused cells and the assessment of Treg activity after infusion.

Several animal studies have demonstrated that infused Treg migrate to transplanted tissue in the early period after transplantation. This finding has important implications for the interpretation of biopsy results in human trials. Recent refinements in Treg identification, quantification, and functional assays will be discussed in the context of immune monitoring.

Understanding the migration/localization and persistence of infused Treg into transplanted tissues as well as how they impact the peripheral immune response will be critical to the interpretation of early Treg trials.