Human CD4+ and CD8+ T lymphocytes are both cytotoxic to Toxoplasma gondii-infected cells

Jose G. Montoya, Karen E. Lowe, Carol Clayberger, Dewey Moody, Duc Do, Jack S. Remington, Sohel Talib, Carlos S. Subauste*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

Studies to determine if Toxoplasma gondii-specific human T cells lyse parasite-infected cells have yielded conflicting results. Furthermore, attempts to obtain human cytotoxic CD8+ T lymphocytes have been difficult because of the lack of a reproducible system for their generation. By using paraformaldehyde-fixed, T. gondii-infected peripheral blood mononuclear cells as antigen-presenting cells, we developed a method whereby T. gondii-specific T-cell lines can be reproducibly generated. Six T. gondii-specific T-cell lines were generated from an individual chronically infected with T. gondii. Cytofluorimetric analysis of these lines revealed >99% CD3+, 85 to 95% CD3+ αβ T-cell-receptor-positive (TCR+), 5 to 9% CD3+ γδ TCR+, 50 to 70% CD4+, and 20 to 40% CD8+ cells when cells were examined during the first 3 weeks of stimulation and >99% CD3+, > 99% CD3+ αβ TCR+, < 1% CD3+ γδ TCR+, 20 to 40% CD4+, and 60 to 80% CD8+ cells when cells were examined between 5 and 11 weeks. Both CD4+ and CD8+ T cells had remarkable cytotoxic activity against T. gondii-infected target cells (30 to 50% specific Cr release at an effector-to-target ratio of 30:1) but not against uninfected target cells (< 10% at an effector-to-target ratio of 30:1). Cytotoxic activity by the whole T-cell lines was not T. gondii strain specific. Whole T-cell lines were cytotoxic for target cells infected with the C56 and ME49 strains and the RH strain (which was used to infect peripheral blond mononuclear cells). T. gondii-specific T-cell lines displayed the predominant expression of Vβ7 TCR. The CDR3 regions of the Vβ7 TCRs of these T-cell lines showed a striking degree of sequence identity (oligoclonality). T-cell lines obtained by the method reported here can be used to characterize functional activity of T-lymphocyte subsets in humans infected with T. gondii.

Original languageEnglish (US)
Pages (from-to)176-181
Number of pages6
JournalInfection and immunity
Volume64
Issue number1
DOIs
StatePublished - 1996

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Human CD4<sup>+</sup> and CD8<sup>+</sup> T lymphocytes are both cytotoxic to Toxoplasma gondii-infected cells'. Together they form a unique fingerprint.

Cite this