3.3 UVB induces alloantigen-specific immunosuppression in mouse model of allogeneic skin transplantation
We employed a mouse model of allogeneic skin transplantation to further investigate the antigen-specific immunosuppression induced by UVB. Full-thickness tail skin grafts from C57BL/6 donor mice were transplanted onto the right chest of BALB/c recipient mice. Starting on day 5, recipient mice were exposed to UVB every other day for a total of 5 courses (Figure 3A). Graft rejection was defined as less than 20% viable tissue remaining. We found that allogeneic skin grafts underwent complete rejection around 30 days post-transplantation, while UVB-treated grafts exhibited delayed rejection kinetics (Figure 3B). Histological analysis revealed reduced immune cell infiltration in UVB-treated grafts (Figure 3C). We further isolated cells from the graft tissues for flow cytometric analyses and found UVB significantly increased the frequency of CD25+Foxp3+ Tregs with enhanced activation markers (ICOS and LAG-3) (Figure 3D). To determine whether UVB-induced immunosuppression in the skin is antigen-specific, a second skin graft (either C57BL/6 or C3H) was transplanted onto the left chest of recipient mice (Figure 3E). In mice without UVB treatment during the first graft, both second grafts (C57BL/6 and C3H) were rejected. However, in mice with UVB treatment during the first graft, the second C3H graft was rejected normally, but the second C57BL/6 graft exhibited prolonged survival (Figure 3F). These results underscore the role of UVB in inducing antigen-specific immunosuppression via antigen-activated Treg induction.