The immunopathology and clinical relevance of lymphocyte cultures in liver transplantation
Kolbeck, P.C.; Wood, R.P.; Markin, R.S.
Modern Pathology An Official Journal of the United States and Canadian Academy of Pathology Inc 6(3): 307-312
1993
ISSN/ISBN: 0893-3952 PMID: 8346179 Document Number: 405305
Lymphocytes infiltrating human liver allograft biopsies were expanded in vitro for 3 to 5 days in recombinant IL-2 and then uniformly quantified 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. Each of the 117 cases was assigned to one of three primary clinical outcome groups based on a retrospective evaluation of the clinical course before and after biopsy. The groups consisted of cases involving viral infection (n = 21), rejection (n = 40), or nonrejection-related allograft dysfunction (n = 56). The rejection group showed significantly greater in vitro expansion of lymphocytes (4201 +- 685) compared to the nonrejection group (2720 +- 408, P lt 0.05). However, cases from the viral infection group showed the highest overall average lymphocyte growth (6655 +- 2595, P lt 0.05). Immunohistologic evaluation of the source liver transplant biopsy demonstrated increased T-cell infiltration of portal triads primarily by CD8+ T-cells in rejection compared to nonrejection cases (semiquantitative grade 1.3 +- 0.1 versus 1.0 +- 0.1, P lt 0.05). The viral infection group demonstrated more significant T-cell infiltration (again predominantly CD8+) of the lobules compared to cases without viral inffection (1.9 +- 0.3 versus 1.3 +- 0.1, P lt 0.05). Immunohistologic evaluation of the cultured lymphocytes from the biopsies demonstrated a marked predominance (75% of cultures) of CD8+ T-cells compared to CD4+ T cells. In addition, lymphocyte growth from 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 (correlation coefficient 0.30, P = 0.02) outcome groups. These results confirm the clinical relevance of biopsy lymphocyte culture results in cases of acute allograft rejection but more importantly suggest a direct role for viral infection in relation to the infiltration and proliferation of 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 source tissue at the time of biopsy.