Mechanisms of allograft and xenograft rejection: possibilities for the future
Allografts are rejected primarily by T lymphocytes. The overall evidence suggests that both CD4+ helper T cells (Th) and CD8+ cytotoxic T cells (Tc) participate in the rejection response. When donor and recipient differ for the major histocompatibility complex in humans, termed HLA, the CD4+ cells respond to HLA class II antigens whereas the CD8+ cells respond to HLA class I antigens. These two cell populations can collaborate in the response. In addition, there can be a response without the CD4+ Th in that CD8+ Tc can, in some cases, make their own helper factors, a cell that is referred to as a helper cell independent cytotoxic T cell. In order to activate the T cell response, the recipient’s T cells must recognize not only the foreign antigen on the antigen presenting cells (APC) of the donor, but also other ligands on those APC. One of the most important of these is the interaction of B7 with CD28. These provide second, or co-stimulatory signals to the responding T cell. Without these, recognition of antigen alone results in anergy of the T cell, which may, in fact, create a state of non- responsiveness that is the basis of one form of tolerance. The ultimate hope for allotransplantation is to get specific tolerance, which can be of one or both of two types.