Toxoplasma gondii-specific CD4+ T cell clones from healthy, latently infected humans display a Th0 profile of cytokine secretion.
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)-gamma, IL-4 and IL-5 upon mitogen or antigen stimulation. Tg-specific T cell clones were classified as T helper of type 0 (Th0) since most of them released roughly comparable amounts of IFN-gamma and IL-4. In some clones, a trend to an increased production of IFN-gamma following antigen-specific as compared to non-specific stimulation was observed. The Th0 phenotype was also expressed by T cell clones that had been raised from bulk cultures performed in the presence of IL-4 or IFN-gamma. 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-gamma. Taken together, these findings suggest that Tg-specific Th0 helper cell clones from healthy, latently infected individuals, beside activating toxoplasmacidal mechanisms through IFN-gamma release, might limit the magnitude of the immune response of the parasite by killing Tg-infected antigen-presenting cells and by releasing IL-10.
Prigione
I
I
Laboratory of Oncology, Scientific Institute G. Gaslini, Genova, Italy.
Facchetti
P
P
Ghiotto
F
F
Tasso
P
P
Pistoia
V
V
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002353:Carrier State / Q000276:immunology*; D002522:Chlorocebus aethiops; D002999:Clone Cells / Q000276:immunology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D007378:Interleukins / Q000096:biosynthesis* / Q000235:genetics; D008213:Lymphocyte Activation; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014122:Toxoplasma / Q000276:immunology*; D014123:Toxoplasmosis / Q000276:immunology*; D014709:Vero Cells / Q000469:parasitology
D000911:Antibodies, Monoclonal; D017077:Culture Media, Conditioned; D006684:HLA-DR Antigens; D007376:Interleukin-2; D007378:Interleukins; D012333:RNA, Messenger; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011994:Recombinant Proteins; D015847:Interleukin-4; D007371:Interferon-gamma