The control of CD8+ T cell responses is preserved in perforin-deficient mice and released by depletion of CD4+CD25+ regulatory T cells

J Leukoc Biol. 2013 Oct;94(4):825-33. doi: 10.1189/jlb.0413200. Epub 2013 Jul 24.


Immune suppression by Treg has been demonstrated in a number of models, but the mechanisms of this suppression are only partly understood. Recent work has suggested that Tregs may suppress by directly killing immune cell populations in vivo in a perforin- and granzyme B-dependent manner. To establish whether perforin is necessary for the regulation of immune responses in vivo, we examined OVA-specific CD8(+) T cell responses in WT and PKO mice immunized with OVA and α-GalCer and the expansion of WT OT-I CD8(+) T cells adoptively transferred into WT or PKO mice immunized with DC-OVA. We observed similar expansion, phenotype, and effector function of CD8(+) T cells in WT and PKO mice, suggesting that CD8(+) T cells were subjected to a similar amount of regulation in the two mouse strains. In addition, when WT and PKO mice were depleted of Tregs by anti-CD25 mAb treatment before DC-OVA immunization, CD8(+) T cell proliferation, cytotoxicity, and cytokine production were increased similarly, suggesting a comparable involvement of CD25(+) Tregs in controlling T cell proliferation and effector function in these two mouse strains. These data suggest that perforin expression is not required for normal immune regulation in these models of in vivo CD8(+) T cell responses induced by immunization with OVA and α-GalCer or DC-OVA.

Keywords: DC vaccines; cytokine production; killing; rodent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / cytology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Differentiation
  • Cell Proliferation
  • Cell Survival
  • Dendritic Cells / metabolism
  • Galactosylceramides / metabolism
  • Immunization
  • Interleukin-2 Receptor alpha Subunit / metabolism*
  • Lectins, C-Type
  • Lymphocyte Depletion*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Ovalbumin / immunology
  • Pore Forming Cytotoxic Proteins / deficiency*
  • Pore Forming Cytotoxic Proteins / metabolism
  • Receptors, Immunologic / metabolism
  • T-Lymphocytes, Regulatory


  • Galactosylceramides
  • Interleukin-2 Receptor alpha Subunit
  • Klrg1 protein, mouse
  • Lectins, C-Type
  • Pore Forming Cytotoxic Proteins
  • Receptors, Immunologic
  • alpha-galactosylceramide
  • perforin, mouse
  • Ovalbumin