Selective Depletion of Alloreactive Cells in Transplantation

Abstract

A major goal in clinical transplantation is to be able to guarantee successful engraftment without incurring any morbidity. Immunosuppressive drug therapies that are currently available are relatively nonspecific in action and must be given indefinitely. Consequently, the whole immune system is punished for the actions of a small minority of its lymphocytes. Too little therapy risks rejection, too much risks infection. What is needed is a therapeutic strategy directed to the antigen-specific (alloreactive) cells themselves. As neither host vs graft (HVG) nor graft vs host (GVH) reactions can occur without T cells, it is appropriate to “take-out” just the alloreactive T cells. In this chapter I shall provide a theoretical framework for how this might be done in the transplant recipient. Although it would be easy to speculate on a vast range of possibilities, the reality of the transplant setting dictates that the chosen therapies should be simple and “low impact”. In other words we would like to achieve therapeutic immunological tolerance with as straightforward a measure as possible and with minimal collateral damage. Certainly transplantation tolerance is an achievable goal in humans (Strober et al. 1989).

The final version of this work was submitted in September, 1991.