Homeostatic regulation of CD8+ T cells by perforin

Eur J Immunol. 1999 Oct;29(10):3262-72. doi: 10.1002/(SICI)1521-4141(199910)29:10<3262::AID-IMMU3262>3.0.CO;2-A.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Viral*
  • CD4 Antigens / biosynthesis
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / virology
  • Down-Regulation / immunology
  • Glycoproteins / administration & dosage
  • Glycoproteins / immunology
  • Homeostasis / immunology*
  • Injections, Intravenous
  • Lymphocyte Activation / immunology
  • Lymphocytic Choriomeningitis / immunology
  • Lymphocytic choriomeningitis virus / immunology
  • Membrane Glycoproteins / deficiency
  • Membrane Glycoproteins / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / immunology
  • Perforin
  • Pore Forming Cytotoxic Proteins
  • Receptors, Antigen, T-Cell, alpha-beta / immunology
  • Superantigens / administration & dosage
  • T-Lymphocytes, Cytotoxic / immunology
  • Viral Proteins*

Substances

  • Antigens, Viral
  • CD4 Antigens
  • Glycoproteins
  • Membrane Glycoproteins
  • Peptide Fragments
  • Pore Forming Cytotoxic Proteins
  • Receptors, Antigen, T-Cell, alpha-beta
  • Superantigens
  • T cell receptor Vbeta8
  • Viral Proteins
  • glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus
  • Perforin