IFN-γ Promotes Fas Ligand- and Perforin-Mediated Liver Cell Destruction by Cytotoxic CD8 T Cells
| Autor: | Hanspeter Pircher, Evelyn Roth |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Cytotoxicity
Immunologic Male Pore Forming Cytotoxic Proteins congenital hereditary and neonatal diseases and abnormalities Adoptive cell transfer Fas Ligand Protein Immunology Mice Transgenic Hepatitis Animal Ligands Lymphocyte Activation Fas ligand Interferon-gamma Mice Interleukin 21 Animals Immunology and Allergy Cytotoxic T cell fas Receptor Mice Knockout Membrane Glycoproteins biology Perforin Liver cell ZAP70 Fas receptor Adoptive Transfer Molecular biology eye diseases Up-Regulation Mice Inbred C57BL Hepatocytes biology.protein Female sense organs Spleen T-Lymphocytes Cytotoxic |
| Zdroj: | The Journal of Immunology. 172:1588-1594 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | To study liver cell damage by CTL, CD8 T cells from P14 TCR transgenic (tg) mice specific for the gp33 epitope of lymphocytic choriomeningitis virus with either deficiency in IFN-γ (P14.IFN-γ°), functional Fas ligand (P14.gld), or perforin (P14.PKO) were transferred into H8 tg mice ubiquitously expressing gp33 Ag. Treatment of H8 recipient mice with agonistic anti-CD40 Abs induced vigorous expansion of the transferred P14 T cells and led to liver cell destruction determined by increase of glutamate dehydrogenase serum levels and induction of caspase-3 in hepatocytes. Liver injury was mediated by the Fas/Fas ligand (FasL) pathway and by perforin, because P14.gld and P14.PKO T cells failed to induce increased glutamate dehydrogenase levels despite strong in vivo proliferation. In addition, H8 tg mice lacking Fas were resistant to the pathogenic effect of P14 T cells. Besides FasL and perforin, IFN-γ was also required for liver cell damage, because P14.IFN-γ° T cells adoptively transferred into H8 mice failed to induce disease. Moreover, Fas expression on hepatocytes from H8 recipient mice was increased after transfer of wild-type compared with P14.IFN-γ° T cells, and wild-type P14 T cells expressed higher levels of FasL than P14 T cells lacking IFN-γ. Thus, our data suggest that IFN-γ released by activated CD8 T cells upon Ag contact facilitates liver cell destruction. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|