Interferon-γ Induced Expression of MHC Antigens Facilitates Identification of Donor Cells in Chimeric Transplant Recipients

Abstract

After whole organ transplantation, donor bone marrow-derived cells migrate out of the graft into the recipient, leading to establishment of chimerism, which is the first step towards the subsequent induction of donor-specific tolerance. In routine immunohistochemical staining, monoclonal antibodies specific for heterotopic MHC alleles are used to identify donor and recipient cells. However, it is difficult to detect these cells using this technique in long-term allograft recipients who have a persistently low donor cell population (microchimerism). Because Interferon-gamma (IFN-γ) is known to induce expression of MHC class I and class II cell surface molecules, we used this cytokine 12-48 h before sacrifice, to facilitate the identification of donor and recipient cells in the tissues of animals transplanted with either liver (B10 → C3H) or bone marrow (LEW → BN). In long-term allograft recipients, the use of IFN-γ for as briefly as 12 h prior to sacrifice, results in marked upregulation of class I and class II antigens, leading to easy identification of ubiquitously distributed low numbers of donor cells.