Monoclonal antibody (mAb) technology has made possible the production
of designer proteins, specifically reactive with almost any conceivabl
e biological molecule. Using these reagents, the surface molecules on
cells crucial for allograft rejection have been identified and describ
ed in detail. These structures can now be selectively targeted by mAb-
based therapy in order to prevent rejection. For instance, the CD3 mol
ecule, expressed on all mature T lymphocytes, triggers T cell activati
on, a key event in rejection. OKT3, an anti-CD3 mAb, disrupts T cell f
unction and is now the agent of choice for the treatment of severe rej
ection episodes. MAbs targeting other T cell molecules are currently b
eing investigated. Some of the most promising, the anti-CD4, anti-ICAM
-1, and anti-interleukin 2 receptor mAbs, have already induced donor-s
pecific tolerance in rodent models. These hosts accept permanently a g
enetically incompatible graft after only a limited period of mAb thera
py. Interestingly, anti-ICAM-1 also diminishes the ischemic injury of
preservation. The development of these new molecular agents, effective
ly directed to specific cellular targets, will likely play an increasi
ngly important role in future clinical protocols, and perhaps finally
provide a means to achieve long-term tolerance in human allograft reci
pients.