Infiltrating cell phenotypes and patterns associated with hepatic allograft rejection or acceptance.

Abstract

The association of inflammatory cell infiltration with orthotopic rat liver transplant rejection was studied by immunopathologic evaluation of allografts at different time points using high- and low-responder strain combinations. PVG(RT-1c) recipients of ACI (RT-1a) liver transplants had prolonged survival (greater than 100 days) without immunosuppression. In contrast, Lewis (RT-1l) recipients of ACI liver transplants had severe acute rejection with mean survival of 10.7 +/- 0.5 days (n = 9). Graft recipients of both strain combinations, as well as control syngeneic PVG-to-PVG and Lewis-to-Lewis graft recipients were sacrificed at various time points posttransplant. Sections of livers were evaluated in a masked fashion for histologic changes as well as the extent and phenotype of cellular infiltrates, as determined by immunoperoxidase labeling using monoclonal antibodies OX1 (pan leukocyte), W3/13 (pan T cell), W3/25 (T helper cell:Th), and OX8 (T cytotoxic-suppressor:Tc-s). The results suggest that: the intensity and relative distribution of rat hepatic allograft T cell infiltrates at a given time point do not necessarily correlate with eventual outcome; the intensities of W3/25 (Th) and OX1 (pan-leukocyte) cell infiltrates parallel each other in both high- and low-responder strain combinations; the relative ratio of T cells (W3/13) to non-T cells increases over time in low-responder strains but remains relatively constant in high-responder strains during active rejection; and the relative ratio of W3/25:OX8 (Th:Tc-s) decreases in high-responder strains but increases in low-responder strains.