MHC class II-expressing hepatocytes function as antigen-presenting cells and activate specific CD4 T lymphocyutes

TY - JOUR

T1 - MHC class II-expressing hepatocytes function as antigen-presenting cells and activate specific CD4 T lymphocyutes

AU - Herkel, Johannes

AU - Jagemann, Bettina

AU - Wiegard, Christiane

AU - Lazaro, Jose Francisco Garcia

AU - Lueth, Stefan

AU - Kanzler, Stephan

AU - Blessing, Manfred

AU - Schmitt, Edgar

AU - Lohse, Ansgar W

PY - 2003/5

Y1 - 2003/5

N2 - The ability to activate CD4 T cells is restricted to antigen-presenting cells that express major histocompatibility complex (MHC) class II molecules. Parenchymal cells normally do not express MHC class II molecules; however, in clinical hepatitis, viral or autoimmune, hepatocytes often exhibit aberrant MHC class II expression. It is not known whether MHC class II-expressing hepatocytes can function as antigen-presenting cells, but it has been suggested that aberrant MHC class II expression by parenchymal cells may cause autoimmune disease. Therefore, we generated transgenic mice that specifically overexpress class II transactivator molecules in hepatocytes. Hepatocytes from these mice exhibited stable MHC class II expression and were used to stimulate CD4 T cells from T-cell receptor transgenic mice and CD4 T-cell lines. MHC II-expressing hepatocytes featured costimulatory CD80 molecules and could serve as antigen-presenting cells that were able to process protein antigen and to activate specific CD4 T cells. Nevertheless, the transgenic mice with aberrant hepatocellular MHC class II expression did not exhibit any symptoms of autoimmune disease. In conclusion, MHC II-expressing hepatocytes, as found in clinical hepatitis, can present antigen and activate CD4 T cells. The ability of hepatocytes to present antigen on MHC II molecules does not seem to be a sufficient cause for inflammatory autoimmunity and hepatitis. However, we still need to explore whether such antigen presentation is occurring in vivo. The transgenic mice described in this study may serve as a model to study the immune interaction of hepatocytes and CD4 T cells in both in vitro and in vivo.

AB - The ability to activate CD4 T cells is restricted to antigen-presenting cells that express major histocompatibility complex (MHC) class II molecules. Parenchymal cells normally do not express MHC class II molecules; however, in clinical hepatitis, viral or autoimmune, hepatocytes often exhibit aberrant MHC class II expression. It is not known whether MHC class II-expressing hepatocytes can function as antigen-presenting cells, but it has been suggested that aberrant MHC class II expression by parenchymal cells may cause autoimmune disease. Therefore, we generated transgenic mice that specifically overexpress class II transactivator molecules in hepatocytes. Hepatocytes from these mice exhibited stable MHC class II expression and were used to stimulate CD4 T cells from T-cell receptor transgenic mice and CD4 T-cell lines. MHC II-expressing hepatocytes featured costimulatory CD80 molecules and could serve as antigen-presenting cells that were able to process protein antigen and to activate specific CD4 T cells. Nevertheless, the transgenic mice with aberrant hepatocellular MHC class II expression did not exhibit any symptoms of autoimmune disease. In conclusion, MHC II-expressing hepatocytes, as found in clinical hepatitis, can present antigen and activate CD4 T cells. The ability of hepatocytes to present antigen on MHC II molecules does not seem to be a sufficient cause for inflammatory autoimmunity and hepatitis. However, we still need to explore whether such antigen presentation is occurring in vivo. The transgenic mice described in this study may serve as a model to study the immune interaction of hepatocytes and CD4 T cells in both in vitro and in vivo.

KW - Animals

KW - Antigen-Presenting Cells/immunology

KW - CD4-Positive T-Lymphocytes/immunology

KW - Gene Expression/immunology

KW - Hepatitis/immunology

KW - Hepatocytes/immunology

KW - Histocompatibility Antigens Class II/genetics

KW - Lymphocyte Activation/immunology

KW - Mice

KW - Mice, Inbred Strains

KW - Mice, Transgenic

KW - Nuclear Proteins

KW - Trans-Activators/genetics

U2 - 10.1053/jhep.2003.50191

DO - 10.1053/jhep.2003.50191

M3 - SCORING: Journal article

C2 - 12717388

VL - 37

SP - 1079

EP - 1085

JO - HEPATOLOGY

JF - HEPATOLOGY

SN - 0270-9139

IS - 5

M1 - 5

ER -