Human cord blood-derived regulatory T-cell therapy modulates the central and peripheral immune response after traumatic brain injury

Abstract

Abstract Traumatic brain injury (TBI) causes a profound inflammatory response within the central nervous system and peripheral immune system, which contributes to secondary brain injury and further morbidity and mortality. Preclinical investigations have demonstrated that treatments that downregulate microglia activation and polarize them toward a reparative/anti-inflammatory phenotype have improved outcomes in preclinical models. However, no therapy to date has translated into proven benefits in human patients. Regulatory T cells (Treg) have been shown to downregulate pathologic immune responses of the innate and adaptive immune system across a variety of pathologies. Furthermore, cellular therapy has been shown to augment host Treg responses in preclinical models; yet, studies investigating the use of Treg as a therapeutic for TBI are lacking. In a rodent TBI model, we demonstrate that human umbilical cord blood Treg modulate the central and peripheral immune response after injury in vitro and in vivo. Significance statement This study demonstrates that human regulatory T cells (Treg) expanded from umbilical cord blood can reduce neuroinflammation associated with traumatic brain injury. A single dose of Treg can cause long-term changes in brain microgliosis in chronic TBI.