Toxoplasma gondii‐specific CD4+ T cell clones from healthy, latently infected humans display a ThO profile of cytokine secretion

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Abstract
Human Toxoplasma gondii (Tg)‐specific T cell clones were raised by infecting peripheral blood mononuclear cells (MNC) from two healthy, latently infected individuals with Tg trophozoites. All of the clones had a CD4+ immunophenotype and produced simultaneously interleukin (IL)‐2, interferon (IFN)‐γ, IL‐4 and IL‐5 upon mitogen or antigen stimulation. Tg‐specific T cell clones were classified as T helper of type 0 (ThO) since most of them released roughly comparable amounts of IFN‐γ and IL‐4. In some clones, a trend to an increased production of IFN‐γ following antigen‐specific as compared to non‐specific stimulation was observed. The ThO phenotype was also expressed by T cell clones that had been raised from bulk cultures performed in the presence of IL‐4 or IFN‐γ. All of the Tg‐specific T cell clones were cytolytic in a non‐specific assay which involves the triggering of the CD3‐T cell receptor (TcR) complex. Some clones specifically lysed an autologous lymphoblastoid cell line (LCL) that had been infected with Tg trophozoites. Finally, most of the Tg‐specific T cell clones produced IL‐10, irrespective of whether they had been raised from bulk cultures incubated in the presence or absence of IL‐4 or IFN‐γ. Taken together, these findings suggest that Tg‐specific ThO helper cell clones from healthy, latently infected individuals, beside activating toxoplasmacidal mechanisms through IFN‐γ release, might limit the magnitude of the immune response to the parasite by killing Tg‐infected antigen‐presenting cells and by releasing IL‐10.