Prolonged acceptance of skin grafts induced by B cells places regulatory T cells on the histopathology scene

the participation of regulatory t (treg) cells in b cell-induced t cell tolerance has been claimed in different models. in skin grafts, naive b cells were shown to induce graft tolerance. however, neither the contribution of treg cells to b cell-induced skin tolerance nor their contribution to the histopathological diagnosis of graft acceptance has been addressed. here, using male c57bl/6 naive b cells to tolerize female animals, we show that skin graft tolerance is dependent on cd25+ treg cell activity and independent of b cell-derived il-10. in fact, b cells from il-10-deficient mice were able to induce skin graft tolerance while treg depletion of the host inhibited 100% graft survival. we questioned how treg cell-mediated tolerance would impact on histopathology. b cell-tolerized skin grafts showed pathological scores as high as a rejected skin from naive, non-tolerized mice due to loss of skin appendages, reduced keratinization and mononuclear cell infiltrate. however, in tolerized mice, 40% of graft infiltrating cd4+ cells were foxp3+ treg cells with a high treg:teff (effector t cell) ratio (6:1) as compared to non-tolerized mice where tregs comprise less than 8% of total infiltrating cd4 cells with a treg:teff ratio below 1:1. these results render treg cells an obligatory target for histopathological studies on tissue rejection that may help to diagnose and predict the outcome of a transplanted organ.