Clonal analysis of liver-infiltrating T cells in patients with LKM-1 antibody-positive autoimmune chronic active hepatitis

Clin Exp Immunol. 1991 May;84(2):297-302. doi: 10.1111/j.1365-2249.1991.tb08164.x.


Autoantibodies against microsomal antigen of liver and kidney (LKM-1) are diagnostic markers for a subgroup of autoimmune chronic active hepatitis (AI-CAH). Cytochrome P450dbl, now classified as cytochrome P450 IID6, is the major antigen of LKM-1 antibodies. Immunohistological studies suggest that hepatic injury in AI-CAH is mediated by liver-infiltrating T cells. In the present study the specificity and function of liver-infiltrating T cells was analysed at the clonal level. Phenotypical characterization of 189 T cell clones isolated from four liver biopsies of LKM-1 antibody-positive patients showed an enrichment of CD4+ CD8- T cell clones proliferated specifically in the presence of recombinant human LKM-1 antigen (rLKM). This reaction was restricted to autologous antigen-presenting cells and to HLA class II molecules. In order to see whether rLKM was also recognized by peripheral blood T lymphocytes (PBL) we tested the proliferative response of PBL from several individuals. PBL from three of the four patients with LKM-1 antibody-positive AI-CAH proliferated to rLKM, whereas no response was seen with PBL from patients with LKM-1 antibody-negative chronic liver diseases and from healthy blood donors. These data demonstrate that the LKM-1 antigen is recognized by liver-infiltrating T cells in LKM-1 antibody-positive AI-CAH. For further functional characterization, liver-derived T cell clones were tested for their cytotoxic activity. In the presence of phytohaemagglutinin 24 out of 26 CD4- CD8+ but also 20 out of 63 CD4+ CD8- T cell clones lysed autologous as well as allogenic EBV-transformed B cell lines or K562 cells. Five CD4- CD8+ T cell clones lysed autologous but not allogenic B cell lines spontaneously in a HLA class I-restricted manner. Although the antigen specificity of these clones is still unknown the data show the presence of autoreactive T cells at the site of inflammation that could contribute in the pathogenesis of AI-CAH.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antigens, CD / analysis
  • Autoantibodies / immunology*
  • Autoimmune Diseases / immunology*
  • Clone Cells
  • Cytotoxicity, Immunologic
  • Female
  • Hepatitis, Chronic / immunology*
  • Humans
  • Immunophenotyping
  • Liver / pathology
  • Lymphocyte Activation / drug effects
  • Male
  • Recombinant Proteins / immunology
  • T-Lymphocytes / immunology*
  • Thymidine / metabolism


  • Antigens, CD
  • Autoantibodies
  • Recombinant Proteins
  • anti-liver kidney microsome antibody
  • Thymidine