TABLE 1.

The effect of ECP on immune cells and their role in graft rejection

Cell type	Role in organ rejection	Effect of ECP on cell fuction
DCs	Direct alloantigen-specific rejection through activation of naive T cells, induces expansion of Teff cells and expression of IL-6, IL-12, and TNF-α89	Secrete IL-10, inhibit Teff cells and induce expansion of Tregs38,90
Macrophages	Increase tissue fibrosis due to excessive expression of TGF-β and expression of TNF-α, IL-6, and IL-1β57,58	Promotes M2 phenotype, induces IL-10 expression, inhibits Teff cells, and induces expansion of Treg60,61
Teff cells	CD4+ T cells orchestrate immune response through expression of cytokines/CD8+ T cells express cytolytic enzymes targeting graft cells91	Dampenes Teff function and inhibits expansion38
Treg	Reduced activity in acute and chronic rejection92	Contributes to graft tolerance, increases Treg expansion, induces expression of IL-10, and reduces Teff function50,53,55,93
NK cells	Recognize and kill allogeneic cells, antibody-mediated cytotoxicity, release cytotoxic enzymes, express proinflammatory cytokines (INF-γ, TNF-α)63	Reduces cytotoxic activity, kills alloreactive T cells, and maintains antiviral and antitumoral activity66,67
B cells	Present antigens to T cells, produce DSAs, expression of proinflammatory cytokines (IL-6, TNF-α)68	Increases regulatory phenotype, inhibits alloreactive T cells through IL-10 and IL-35 expression, and reduces antigen presentation in DCs and macrophages68,72,73
MDSCs	Immunosuppressive regimens affect MDSC numbers and potentially reduce their immunoregulatory capacity85,86	Strong suppressive effect on Teff cells81-83

DC, dendritic cell; DSA, donor-specific antibody; ECP, extracorporeal photopheresis; IFN, interferon; IL, interleukin; MDSC, myeloid-derived suppressor cell; NK, natural killer; T_eff cell, effector T cell; TGF, transforming growth factor; TNF, tumor necrosis factor; Treg, regulatory T cell.