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Publication : Cell-mediated cytotoxicity in perforin-less mice.

First Author  Clark WR Year  1995
Journal  Int Rev Immunol Volume  13
Issue  1 Pages  1-14
PubMed ID  7494105 Mgi Jnum  J:31057
Mgi Id  MGI:78518 Doi  10.3109/08830189509061734
Citation  Clark WR, et al. (1995) Cell-mediated cytotoxicity in perforin-less mice. Int Rev Immunol 13(1):1-14
abstractText  We have used a perforin-less (PO) mouse to explore alternate CTL-mediated lytic pathways. PO mice are unable to overcome an infection with LCMV in vivo. Nevertheless, splenocytes from infected mice show vigorous, antigen-specific cytotoxicity that requires the presence of the Fas antigen on target cells. The Fas lytic pathway is virtually indistinguishable, in terms of kinetics and magnitude of cytotoxicity, from perforin/granzyme-mediated lysis. It is rapidly induced in CTL upon occupation of the TcR, and requires protein synthesis for full expression. Upon removal of the activating signal, the capacity for fas-mediated lysis rapidly disappears. PO mice infected with LCMV also undergo what appears to be a CD8-mediated immunopathology, and rarely live beyond one month. The precise basis of this pathology is unknown at present. Given the widespread distribution of Fas in mice, particularly on inflamed tissues, the complete failure to clear virus from any tissue or organ is surprising.
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