ABSTRACT

T-cells can be physiologically silenced by various mechanisms in­ cluding anergy, central deletion in the thymus, deletion in the peripheral immune system and immune suppression.8 An improved understanding of these mechanisms may lead to novel strategies to induce transplant tolerance by inhibiting alloreactive T-cells.1 Solid organ transplants contain rare nonparenchymal cells, i.e., interstitial “passenger” leuko­ cytes that can migrate into the recipient and establish long-lasting microchimerism, defined as the persistence of a small number of donor bone marrow (BM)-derived cells in the recipient.9 Although such microchimerism is often associated with graft acceptance and tolerance, it has been difficult to demonstrate a true causal link. In a skin transplantation model using mutant mice deficient for leukocyte subsets, donor T-cell chimerism resulted in very different outcomes

depending on the host s immunological maturity and the antigenic disparities involved.10 In immunologically mature hosts, chimerism enhanced immunity and graft rejection, whereas in immature hosts, it induced tolerance to the chimeric T-cells, but not to graft antigens not expressed by the chimeric cells.