Perforin knockout mice retain cd8+ t lymphocyte immunity to toxoplasma gondii despite absence of parasite-specific ctl function

E. Y. Denkers, G. Yap, H. Charest, T. Scharton-Karsten, B. A. Butcher, A. Sher

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Wild-type (WT) mice vaccinated with the attenuated parasite strain ts-4 develop CD8+ and IFN-γ based immunity to challenge with the virulent parasite strain RH, but the contribution of perforin-dependent CD8+ CTL activity has until now been impossible to evaluate. In order to determine the role of the latter CD8 effector function during T. gondii infection, gene targeted perform knockout (KO) animals were ts-4 vaccinated, then challenged with RH. KO and WT mice survived up to 60 d following challenge, whereas nonvaccinated animals of both strains succumbed 10-14 d after RH infection. In vitro assays demonstrated that KO, in contrast to WT, animals totally lack parasite-specific CTL function against tachyzoite-infected macrophages. In addition, parasite-induced NK cell lytic activity against YAC-1 targets, demonstrable in WT mice, was completely absent in perform KO animals. In cultures of splenocytes stimulated with parasite Ag, high levels of IFN-γ were released by cells from both WT and KO animals. Our results demonstrate that perform is not required for expression of resistance to T. gondii, and suggest that CTL activity, in marked contrast to IFN-γ production, does not play a significant role in the protective function of CD8+ T lymphocytes during T. gondii infection.

Original languageEnglish (US)
Pages (from-to)A1018
JournalFASEB Journal
Volume10
Issue number6
StatePublished - Dec 1 1996
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Fingerprint Dive into the research topics of 'Perforin knockout mice retain cd8+ t lymphocyte immunity to toxoplasma gondii despite absence of parasite-specific ctl function'. Together they form a unique fingerprint.

  • Cite this

    Denkers, E. Y., Yap, G., Charest, H., Scharton-Karsten, T., Butcher, B. A., & Sher, A. (1996). Perforin knockout mice retain cd8+ t lymphocyte immunity to toxoplasma gondii despite absence of parasite-specific ctl function. FASEB Journal, 10(6), A1018.