Impairment of T cell interactions with antigen-presenting cells by immunosuppressive drugs reveals involvement of calcineurin and NF-kappaB in immunological synapse formation.
Skin, an important component of composite tissue allografts is considered to be among the most immunogenic of tissues. The mechanisms of resistance of skin allografts to pharmacological immunosuppression remain unknown. We investigated this problem at the level of antigen presentation by graft dendritic cells (DC) to recipient lymphocytes (L). Cells obtained from lymph draining skin were examined for formation of synapses, necessary for antigen presentation, in the presence of cyclosporine (CsA) or tacrolimus (FK 506). In culture the frequency of DC-L synapses was greater in allogeneic than syngeneic combinations. Cells treated with FK 50% showed a decreased rate of formation of autologous or allogeneic DC-L synapses and lower expression of CD49d. The suppressive effect of FK 506 on DC-L synapse formation may explain the effectiveness of this drug for skin allograft survival.