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IFN-γ Promotes Fas Ligand- and Perforin-Mediated Liver Cell Destruction by Cytotoxic CD8 T Cells
| Content Provider | Semantic Scholar |
|---|---|
| Author | Roth, Evelyn Pircher, Hanspeter |
| Copyright Year | 2004 |
| Abstract | 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. |
| Starting Page | 1588 |
| Ending Page | 1594 |
| Page Count | 7 |
| File Format | PDF HTM / HTML |
| DOI | 10.4049/jimmunol.172.3.1588 |
| Volume Number | 172 |
| Alternate Webpage(s) | http://www.jimmunol.org/content/jimmunol/172/3/1588.full.pdf |
| Alternate Webpage(s) | https://doi.org/10.4049/jimmunol.172.3.1588 |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
