Formation of synapses between dendritic cells and lymphocytes in skin lymph in an allogeneic reaction

Skin is an important component of a composite tissue allograft and is considered among the most immunogenic of tissues. Because of the skin's high degree of immunogenicity, until recently it was widely assumed that the dosage of immunosuppressive drugs required to prevent rejection was too high to be used safely in the clinical setting. The mechanism of resistance of skin allografts to pharmacological immunosuppression remains unknown. We investigated this problem at the level of antigen presentation by graft dendritic cells to recipient lymphocytes. Cells obtained from lymph draining skin were used and formation of synapses, necessary for antigen presentation, in the presence of CsA or FK506 was studied. The study provided the following information: a) increased frequency of allogeneic compared to syngeneic DC-L synapses in culture, b) increased expression of CD49d on lymph allogeneic DC and L and of HLA DR on L forming synapses, c) lack of a downregulating effect of CsA on the allogeneic DC-L synapse formation rate, d) decreased formation rate of autologous and allogeneic DC-L synapses and lower expression of CD49d and HLA DR of cells treated with FK506. The suppressive effect of FK506 on DC-L synapses formation may explain the mechanism of effectiveness of this drug on skin allograft survival.