Figure 6.

Peripheral regulatory mechanism that controls the development of GVHD. The development of GVHD is characterized by activation of T donor cells. Donor T cell activation results mainly in IFNγ and IL-17 production; the IFNγ promotes the increase of MHC, adhesion molecules, nitric oxide release, and vasodilation and increased permeability. This results in further increases in antigen presentation and activation and expansion of cytotoxic CD8⁺ and CD4⁺ T cells; these cells migrate to the target organs, where they mediate tissue injury that leads to multiorgan failure. Nevertheless, there are subpopulations that can intervene at different stages of GVHD and control it; the subpopulation named CD8⁺ Treg can intervene and block activation and expansion of effector cells, through IL-10 and TGFβ production and expression of CD39; these cells reduce the inflammatory state.