Cloned human CD4+ cytotoxic T lymphocytes specific for Toxoplasma gondii lyse tachyzoite-infected target cells

Tyler J Curiel, Edward C. Krug, Matthew B. Purner, Pascal Poignard, Randolph L. Berens

Research output: Contribution to journalArticle

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Abstract

Infection with Toxoplasma gondii is an important cause of morbidity and mortality throughout the world. In immunocompetent hosts, the infection is usually not significant. However, infection occurring in neonates or other individuals with defective cellular immunity (such as recipients of organ allografts or persons with AIDS) may be life threatening. An effective vaccine to prevent toxoplasmosis, or immunotherapy for persons already infected with Tg would be important additions to the therapeutic armamentarium. We cloned toxoplasma-specific CTL from the PBMC of an asymptomatic individual with serologic evidence for prior Tg infection by stimulation with Ag produced from the RH strain of Tg. These CTL were exclusively of the CD8+, CD4+, CD8- surface phenotype, and lysed autologous target cells that had been either pulsed with Toxoplasma Ag, or infected with live tachyzoites. Lysis of target cells was inhibited by incubation of CTL with anti-T cell antibody, or by incubation of target cells with anti-DR antibody or chloroquine. These CTL also lysed target cells either pulsed with Ag derived from C strain Tg or infected with live C strain tachyzoites, indicating cross-reactivity of recognition. Unlike recently reported murine or human CD8+ Tg-specific CTL, which lysed tachyzoites in an extracellular, and hence HLA-unrestricted environment, these CD4+ CTL had no effect on the infectivity of extracellular tachyzoites. CD8+ Tg-specific CTL were not derived from this donor despite several different approaches to their generation. These data confirm previous reports of human Tg-specific CTL, and extend these observations to include CD4+ CTL. These findings suggest that specific immunotherapy directed against Tg, as well as the development of a preventive vaccine, may be possible.

Original languageEnglish (US)
Pages (from-to)2024-2031
Number of pages8
JournalJournal of Immunology
Volume151
Issue number4
StatePublished - Aug 15 1993
Externally publishedYes

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Toxoplasma
Cytotoxic T-Lymphocytes
Toxoplasmosis
Immunotherapy
Vaccines
Infection
Chloroquine
Cellular Immunity
Allografts
Anti-Idiotypic Antibodies
Acquired Immunodeficiency Syndrome
Morbidity
T-Lymphocytes
Phenotype
Mortality
Antibodies
Therapeutics

ASJC Scopus subject areas

  • Immunology

Cite this

Cloned human CD4+ cytotoxic T lymphocytes specific for Toxoplasma gondii lyse tachyzoite-infected target cells. / Curiel, Tyler J; Krug, Edward C.; Purner, Matthew B.; Poignard, Pascal; Berens, Randolph L.

In: Journal of Immunology, Vol. 151, No. 4, 15.08.1993, p. 2024-2031.

Research output: Contribution to journalArticle

Curiel, Tyler J ; Krug, Edward C. ; Purner, Matthew B. ; Poignard, Pascal ; Berens, Randolph L. / Cloned human CD4+ cytotoxic T lymphocytes specific for Toxoplasma gondii lyse tachyzoite-infected target cells. In: Journal of Immunology. 1993 ; Vol. 151, No. 4. pp. 2024-2031.
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