The pattern and phenotype of T-cell infiltration associated with human liver allograft rejection

Although transplant biopsy remains the best means for assessing liver allograft dysfunction, the presence and degree of rejection often is difficult to determine by current histologic criteria. The added diagnostic and prognostic value of examining liver allograft biopsy specimens by immunopathologic methods, such as phenotyping inflammatory cell infiltrates, has been inconclusive. To examine the value of assessing the phenotype and location of T-cell infiltrates we compared findings in 20 liver transplant biopsy specimens obtained from patients undergoing allograft rejection with those in 20 biopsy specimens from patients with no evidence of rejection. Serial frozen sections from all biopsies were labeled by immunoperoxidase techniques using monoclonal antibodies to identify cells expressing CD3, CD4, CD8, CD45RA, and CD45RO. As expected, the median of average cell infiltrates was higher in the rejecting versus nonrejecting group for each cell phenotype and region. However, statistical comparisons indicated that only some combinations of cell phenotype and location were significantly greater in the rejecting versus nonrejecting groups. The median number of portal CD3+ T cells per high-power field was increased in the rejecting versus nonrejecting groups (15.15 v 5.00 cells/high-power field; P < .01). This primarily was the result of a significant increase in CD8+ cells (7.15 v 1.55 cells/high-power field; P < .0001). Examination of cells expressing CD45 isoforms also revealed a suggested increase (P < .04) in CD45RO+ "memory" but not in CD45RA "naive" T cells infiltrating portal areas. In lobular areas cell infiltrates of any examined phenotype were not significantly increased in the rejecting versus nonrejecting groups. These findings indicate that during liver allograft rejection the most characteristic changes involve an increase in T cells infiltrating the graft in portal regions and suggest that human liver allograft rejection preferentially involves memory CD8+ T cells directed at portal structures.