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

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.
A rat model of traumatic brain injury was used to determine whether regulatory T cells (Treg) could be used to treat neuroinflammation associated with severe central nervous system trauma. We utilized multicolor flow cytometry 30d after injury to rapidly assess the changes in the phenotype of microglia, which were visualized using a dimensional reduction algorithm (t‐distributed stochastic neighbor embedding). This method clearly maps populations that change as a result of injury but respond to Treg treatment. Further analysis demonstrates that these particular populations express microglia markers that change in expression levels in response to injury, including CD11bc (pictured here). This response is ameliorated by Treg treatment 24 hours after injury.