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Immune function in mice lacking the perforin gene

C M Walsh1, M Matloubian, C C Liu

  • 1Department of Biology, University of California, Los Angeles 90024.

Proceedings of the National Academy of Sciences of the United States of America
|November 8, 1994
PubMed
Summary
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Mice lacking the perforin gene could not clear lymphocytic choriomeningitis virus (LCMV) infection. The Fas lytic pathway was retained but insufficient for viral clearance in vivo.

Area of Science:

  • Immunology
  • Virology
  • Molecular Biology

Background:

  • Perforin is a key protein in the immune system's cytotoxic response.
  • Cytotoxic T lymphocytes (CTLs) play a crucial role in viral clearance.
  • The Fas pathway is an alternative cytotoxic mechanism.

Purpose of the Study:

  • To investigate the role of perforin in viral clearance using a mouse model.
  • To determine if the Fas pathway can compensate for the lack of perforin during viral infection.
  • To assess the in vivo efficacy of the Fas lytic pathway.

Main Methods:

  • Generation of perforin-deficient mice using gene targeting.
  • Infection of mice with lymphocytic choriomeningitis virus (LCMV).
  • Analysis of immune responses, including CD8 T cell activation and cytotoxic activity in vitro and in vivo.

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  • Assessment of Fas antigen expression on target cells.

    • Main Results:

    • Perforin-deficient mice mounted an immune response but failed to clear LCMV infection.
    • Spleen cells from these mice could not lyse LCMV-infected fibroblasts in vitro.
    • Spleen cells showed Fas-dependent lysis of hematopoietic cells in vitro after stimulation.
    • The Fas pathway was insufficient for complete viral clearance in vivo.

    Conclusions:

    • Perforin is essential for effective clearance of LCMV infection in mice.
    • While the Fas lytic pathway is functional in perforin-deficient mice, it is insufficient for in vivo viral elimination.
    • These findings highlight the critical role of perforin in cell-mediated immunity against viral pathogens.