Ultraviolet-induced alloantigen-specific immunosuppression in transplant immunity

Abstract

After the first observation of the immunosuppressive effects of ultraviolet (UV) irradiation was reported in 1974, therapeutic modification of immune responses by UV irradiation began to be investigated in the context immunization. UV-induced immunosuppression is via the action of regulatory T cells (Tregs). Antigen-specific Tregs were induced by high-dose UV-B irradiation before antigen immunization in many studies, as it was considered that functional alteration and/or modulation of antigen-presenting cells by UV irradiation was required for the induction of antigen-specific immunosuppression. However, it is also reported that UV irradiation after immunization induces antigen-specific Tregs. UV-induced Tregs are also dominantly transferable, with interleukin-10 being important for UV-induced immunosuppression. Currently, various possible mechanisms involving Treg phenotype and cytokine profile have been suggested. UV irradiation accompanied by alloantigen immunization induces alloantigen-specific transferable Tregs, which have potential therapeutic applications in the transplantation field. Here we review the current status of UV-induced antigen-specific immunosuppression on the 40(th) anniversary of its discovery.

Keywords: Alloantigen; Donor-specific immunosuppression; Interleukin-10; Regulatory T cells; Ultraviolet irradiation.

Figure 1

Schema illustrating the postulated reactions in achieving alloantigen-specific immunosuppression by ultraviolet-B irradiation accompanied with alloantigen immunization. APCs, such as mature DC and LC, capture alloantigen. UV-B irradiation and subsequent IL-10 secretion will cause antigen presentation in a nonprofessional manner to induce antigen-specific immunosuppression. Immature DC presents alloantigen to CD4⁺ T cell, and then, Treg induction and IL-10 secretion arise. LC presents alloantigen to NKT cell, and IL-4 secretion subsequently occurs. Also, LC presents alloantigen to Foxp3⁺ Treg, and thereafter, Foxp3⁺ Treg proliferation and Treg induction are triggered. Hence, alloantigen-specific Treg, Foxp3⁺ Treg, IL-10 and IL-4 will regulate allo-immune responses. MHC: Major histocompatibility complex; TCR: T cell receptor; CD: Cluster of differentiation; DEC: Dendritic and epithelial cells; APCs: Antigen-presenting cells; UV: Ultraviolet; DC: Dendritic cell; LC: Langerhans cell; IL: Interleukin; NKT: Natural killer T.