HLA antigen expression and cellular infiltrate analysis in rejected and accepted human liver allografts

A. Nocera, R. Pellicci, S. Barocci, U. Valente, S. Cantarella, F. Celada, F. Callea, P. Ceppa, A. Leprini

Research output: Contribution to journalArticlepeer-review

Abstract

HLA class I (A, B, C) and class II (DP, DQ, DR) antigen expression patterns and mononuclear cell infiltrates were analyzed in liver allograft needle biopsies from 4 acute rejections and 2 stably accepted grafts. Acute rejections were represented by a steroid-resistant irreversible rejection, by a severe rejection responsive only to OKT3 mAb treatment and by 2 reversible moderate rejections. From one of these latter cases, as well as from another patient, liver biopsies were also available 310 and 275 days after transplantation in the presence of a stable graft acceptance. Paraffin and/or cryostat biopsy sections were studied by means of indirect immunohistological techniques using a battery of monoclonal antibodies. Cell lines were also established in vitro by culturing biopsy fragments in recombinant IL-2 and were analyzed for phenotype and donor-specific functions. The results demonstrated that: i) severe rejections were associated with a strong increase of HLA class I antigens on graft parenchymal cells (hepatocytes and bile duct epithelia) and with a DR positivity displayed mainly on bile duct epithelia. Both portal and lobular areas were found to be infiltrated by mononuclear cells constituted mostly by CD8+ T cells endowed with donor-specific CTL activity; ii) moderate rejections were characterized by different class I and DR positivity patterns and by portal cell infiltrates containing high numbers of noncytotoxic CD4+ T cells expressing in vitro donor-specific proliferative activity; iii) mononuclear cell infiltrates of lesser intensity, mostly constituted by CD4+ T cells, were also detected in biopsies from accepted grafts, and these appeared almost normal for histology and for HLA antigen expression pattern. In one of the 2 accepted liver grafts, biopsy-derived non-cytotoxic CD4+ T cells, capable of donor-specific proliferation, could also be expanded in vitro. Other molecules, such as DP and DQ, were never detected on hepatocytes in any of the cases and appeared weakly induced on bile duct epithelium only in severe rejections. These data demonstrate that presence and intensity of rejections as well as graft acceptance may be associated in transplanted livers with distinct patterns of HLA antigen expression and with T-cell infiltrates having different phenotype and function.

Original languageEnglish
Pages (from-to)23-32
Number of pages10
JournalClinical Transplantation
Volume5
Issue number1
Publication statusPublished - 1991

Keywords

  • acute rejection
  • CTL activity
  • graft infiltrating cells
  • HLA antigens
  • Liver transplant
  • T-cell lines

ASJC Scopus subject areas

  • Immunology
  • Transplantation

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