CLONED HUMAN CD4-LYMPHOCYTES SPECIFIC FOR TOXOPLASMA-GONDII LYSE TACHYZOITE-INFECTED TARGET-CELLS( CYTOTOXIC T)

Infection with Toxoplasma gondii is an important cause of morbidity an d mortality throughout the world. In immunocompetent hosts, the infect ion is usually not significant. However, infection occurring in neonat es or other individuals with defective cellular immunity (such as reci pients of organ allografts or persons with AIDS) may be life threateni ng. An effective vaccine to prevent toxoplasmosis, or immunotherapy fo r 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 CD3+, CD4+, CD8- surface phenotype, and lysed autologous target cells that had been either pulsed with To xoplasma Ag, or infected with live tachyzoites. Lysis of target cells was inhibited by incubation of CTL with anti-T cell antibody, or by in cubation of target cells with anti-DR antibody or chloroquine. These C TL also lysed target cells either pulsed with Ag derived from C strain Tg or infected with live C strain tachyzoites, indicating cross-react ivity 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 infe ctivity of extracellular tachyzoites. CD8+ Tg-specific CTL were not de rived from this donor despite several different approaches to their ge neration. These data confirm previous reports of human Tg-specific CTL , and extend these observations to include CD4+ CTL. These findings su ggest that specific immunotherapy directed against Tg, as well as the development of a preventive vaccine, may be possible.