Specific down-regulation of allograft reactivity at the cellular level: graft cells and responder T cells.

Abstract

Local immune reactivity in an allograft is largely determined by (1) the immunogenicity of the grafted cells and (2) the presence of recipient allospecific T lymphocytes and, much more importantly, their capacity to react and initiate damage to the graft. Ad (1): It is still widely believed that allograft immunogenicity is sufficiently described by the cell surface expression of transplantation antigens, in particular MHC class I and II molecules. In extension of earlier, more complex models it will be demonstrated that transfected subclones of a macrophage cell line show unaltered, strong MHC expression but have become non-immunogenic and, most importantly, have acquired the capacity to render mature naive T cells anergic in a specific fashion. Ad (2): Starting from the above and from other observations, we have found in human organ graft recipients that cytotoxic T lymphocyte (CTL) frequencies may be specifically down-regulated but may regain their reactivity after cultivation under ex vivo conditions. In keeping with the latter we can now show quantitatively the variable presence and the functional potential of cell-released (soluble) human MHC (HLA class I) molecules: they are able to specifically inhibit human CTL reactivity in a dose-dependent fashion. Taken together, it may be concluded that studies at the cellular level, in particular the level of human cells, will increasingly help us to better understand and manipulate the immunological interplay between the local graft cell and its most important antagonist, the T lymphocyte.