THE IMMUNOPATHOLOGY AND CLINICAL RELEVANCE OF LYMPHOCYTE-CULTURES IN LIVER-TRANSPLANTATION

Lymphocytes infiltrating human liver allograft biopsies were expanded in vitro for 3 to 5 days in recombinant IL-2 and then uniformly quanti fied and phenotypically characterized. The extent of proliferation was correlated with the degree and pattern of lymphocyte infiltration of the source biopsy as well as with the subsequent clinical outcome. Eac h of the 117 cases was assigned to one of three primary clinical outco me groups based on a retrospective evaluation of the clinical course b efore and after biopsy. The groups consisted of cases involving viral infection (n = 21), rejection (n = 40), or nonrejection-related allogr aft dysfunction (n = 56). The rejection group showed significantly gre ater in vitro expansion of lymphocytes (4201 +/- 685) compared to the nonrejection group (2720 +/- 408, P < 0.05). However, cases from the v iral infection group showed the highest overall average lymphocyte gro wth (6655 +/- 2595, P < 0.05). Immunohistologic evaluation of the sour ce liver transplant biopsy demonstrated increased T-cell infiltration of portal triads primarily by CD8+ T-cells in rejection compared to no nrejection cases (semiquantitative grade 1.3 +/- 0.1 versus 1.0 +/- 0. 1, P < 0.05). The viral infection group demonstrated more significant T-cell infiltration (again predominantly CD8+) of the lobules compared to cases without viral infection (1.9 +/- 0.3 versus 1.3 +/- 0.1, P < 0.05). Immunohistologic evaluation of the cultured lymphocytes from t he biopsies demonstrated a marked predominance (75% of cultures) of CD 8+ T-cells compared to CD4+ T-cells. In addition, lymphocyte growth fr om the biopsies correlated with the infiltration of both portal triads and lobules by CD8+ but not CD4+ T-cells in cases from both the viral (correlation coefficient 0.69, P = 0.01) and the nonviral (correlatio n coefficient 0.30, P = 0.02) outcome groups. These results confirm th e clinical relevance of biopsy lymphocyte culture results in cases of acute allograft rejection but more importantly suggest a direct role f or viral infection in relation to the infiltration and proliferation o f lymphocytes within allografts. In addition, this study demonstrated that biopsy cultures may favor the outgrowth of lobular CD8+ T-cells, thus misrepresenting the actual T-cell infiltrates present in the sour ce tissue at the time of biopsy.