Homeostatic regulation of CD8+ T cells by perforin

✍ Scribed by David Kägi; Bernhard Odermatt; Tak W. Mak

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 273 KB
• Volume: 29
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/(sici)1521-4141(199910)29:10<3262::aid-immu3262>3.0.co;2-a

✦ Synopsis

To prevent uncontrolled expansion, the massive proliferation of T cells during an acute immune response has to be followed by controlled deletion. Here we show that similar to Fas, perforin is not only an important effector molecule of cytotoxic T lymphocytes (CTL) but also involved in down-regulating peripheral T cells. Mice deficient for both the CTL effector molecule perforin and the apoptosis-inducing Fas ligand spontaneously develop infiltration of highly activated CD8 + T cells in kidney and liver and die between 5 and 12 weeks of age. Injection of staphylococcal enterotoxin B (SEB) into perforin-deficient mice results in dramatically increased selective expansion and prolonged persistence of CD8 + , but not CD4 + , SEB-reactive T cells. Also, secondary immunization of TCR transgenic perforin-deficient mice with the lymphocytic choriomeningitis virus glycoprotein-derived epitope peptide leads to an increased proliferation of transgenic CD8 + T cells, that is not explained by failure to deplete professional antigen-presenting cells. These results point to a novel mechanism of T cell homeostasis in which the acquisition of perforin-dependent cytotoxic activity regulates the expansion and persistence of CD8 + effector T cells in vivo.