Figure 4. Balance between Alloreactive T cells and Tregs in transplant outcome.
In the natural state, without any immunosuppression, there is a significantly greater frequency of directly alloreactive T cells that overcome the tolerogenic potential of Tregs and lead to allograft rejection. Administration of immunosuppression eliminates a significantly proportion of directly alloreactive T cells as well as Tregs. Nevertheless, there is influx of donor alloantigens through the indirect pathway that maintains alloreactive T cells. Since indirectly alloreactive T cells are more resistant to immunosuppression, the long-term sequelae of this influx is chronic rejection. Some important factors that can favor Tregs or alloreactive T cells following transplantation are represented.