Clonal analysis of liver-infiltrating T cells in patients with LKM-1 antibody-positive autoimmune chronic active hepatitis
| Autor: | AW Lohse, Michael Manns, B. Fleischer, K H Meyer zum Büschenfelde, Hanns F. Löhr, A. Kyriatsoulis, C. Trautwein |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
Adult
Cytotoxicity Immunologic Male Adolescent T-Lymphocytes T cell Immunology Biology Lymphocyte Activation Autoimmune Diseases Immunophenotyping Interleukin 21 Antigen Antigens CD medicine Humans Immunology and Allergy Cytotoxic T cell Antigen-presenting cell B cell Autoantibodies Hepatitis Chronic Natural killer T cell Recombinant Proteins Clone Cells medicine.anatomical_structure Liver Female CD8 Research Article Thymidine |
| Zdroj: | Clinical and Experimental Immunology. 84:297-302 |
| ISSN: | 1365-2249 0009-9104 |
| DOI: | 10.1111/j.1365-2249.1991.tb08164.x |
| Popis: | SUMMARY Autoantibodies against microsomal antigen of liver and kidney (LKM-1) are diagnostic markers for a subgroup of autoimmune chronic active hepatitis (AI-CAH). Cytochrome P4S0dbl, 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 cells. Five 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 phytohacmagglutinin 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|