TOLERANCE AND LATENT CELLULAR REJECTION IN LONG-TERM LIVER-TRANSPLANTRECIPIENTS

Tolerance develops in a proportion of long-term liver transplant recip ients but currently cannot be identified before an attempt at withdraw al from immunosuppression therapy. In the present study, we have exami ned the immunophenotypic characteristics of the cellular infiltrate in portal tracts and lobules as observed in liver biopsy specimens in re lation to the outcome of subsequent withdrawal from immunosuppression therapy. Cryostat biopsy specimens from 27 lone-term recipients before drug withdrawal, and from 10 patients with recent transplants who wer e having acute rejection, were analyzed. Immunohistochemical staining was performed for CD3(+) (pan T cell), CD8(+) (cytotoxic), CD4(+) (hel per), CD4SRO(+) (memory), CD45RA(+) (naive), CD56(+) (natural killer), CD68(+) (macrophage), and CD8(+) perforin(+) cells. Fewer CD8(+) and CD3(+) cells were present in the lobular areas of biopsy specimens fro m patients who were successfully withdrawn from immunosuppression ther apy (n = 6) compared with biopsy specimens from patients with nontoler ant grafts (n = 9; 15 vs. 23 cells/high-power field [hpf] [P < .01] an d 16 vs. 26 cells/hpf [P < .03], respectively) or biopsy specimens obt ained during acute rejection (15 vs. 31 cells/hpf [P < .01] and 16 vs. 32 cells/hpf [P < .01]), Cell frequencies in the biopsy specimens of nontolerant long-term patients were similar to those found with acute rejection. Immunophenotyping the lobular inflammation within long-term liver allografts assists in identifying those patients in whom drug w ithdrawal is likely to be unsuccessful and in whom it is postulated a form of inactive, latent cellular rejection exists.