The purpose of this study is to explore the potential of prolonging renal allograft survival in sheep by employing donor clonal deletion in the recipient animal by peripheral node stimulation with donor cells (lymphocytes) and removal of the reactive lymph by chronic efferent lymphatic cannulation of the stimulated node. This approach is based on the observation by Hall et al (J. Exp. Med. 125:91, 1967) that immune responses to specific antigens could be confined to the antigenically stimulated node by diverting the efferent lymph and its contained cells from the body by chronic cannulation of the efferent lymphatic of the stimulated node and on observations by Lachmann et al (Nature 250:113, 1974 and J. Exp. Med. 153:706, 1981) that specific abrogation of an established immune response in sheep could be achieved by removing in vivo most of the immunocompetent lymphocytes reactive against the specific antigen by chronic efferent lymphatic drainage of a single peripheral lymph node whose drainage area was being challenged repeatedly by subcutaneous injections with the specific antigen. In the present proposed study, with neck placed renal allografts in sheep, the single node approach of Lachmann et al will be explored and these studies expanded by using multiple simultaneous node cannulations and drainage area stimulations and by the further addition of lymphocyte traffic enhancing measures shown by the PI to be effective in sheep.
Showing the most recent 10 out of 13 publications
