Regulatory T cells as modulators of chronic allograft dysfunction

Chronic allograft dysfunction (CAD) in solid organ transplantation is a principal cause of patient morbidity and late allograft loss. The pathogenesis of CAD is largely secondary to chronic damage by the adaptive immune system and long-term immunosuppression. Manipulating these factors may be possible with the use of regulatory T cells (Treg), which have the ability to suppress specific immune responses and therefore potentially remove the need for immunosuppressive drugs. Studies of CAD in experimental models have demonstrated the capacity for both mouse and human Treg cellular therapy to prevent the development of some manifestations of CAD. Furthermore, a role for Treg has been demonstrated in clinically tolerant transplant patients. Certain immunosuppressive therapies are also proving to be 'Treg friendly' and may be helpful in promoting Treg while maintaining other immunosuppressive activity. With this in mind, monitoring for biomarkers of operational tolerance with tailored immunosuppressive therapy or controlled weaning in conjunction with Treg cellular therapy may be a useful strategy to pursue.