Establishment of T-helper type 1- and T-helper type 2-like human Toxoplasma antigen-specific T-cell clones.
As an in vitro model for human cerebral toxoplasmosis, we analysed the interaction between glioblastoma cells, Toxoplasma and Toxoplasma antigen-specific T-helper cells. We established 46 different human CD4+ T-cell clones from four different donors. All T-cell clones responded to Toxoplasma antigen derived from three different Toxoplasma strains. We found that the supernatants of 44 clones induced toxoplasmostasis in glioblastoma cells. The anti-parasitic effector mechanism activated in glioblastoma cells by T-cell supernatants was the induction of the tryptophan-degrading enzyme indolamine 2,3-dioxygenase. Enzyme induction, as well as the anti-parasitic effect, was blocked by a monoclonal antibody directed against interferon-gamma (IFN-gamma), and the addition of L-tryptophan to the cultures completely blocked the anti-parasitic effect induced by T-cell supernatants. The supernatants from two of the 46 established T-cell clones (3A22 and 1A15) were unable to induce indolamine 2,3-dioxygenase activity or, as expected, toxoplasmostasis in glioblastoma cells. We further analysed the supernatants from these two clones, and found that they contained large amounts of IL-4 and no, or only limited amounts of, IFN-gamma. We therefore conclude that Toxoplasma-antigen is able to activate T-helper type 1 (Th1)- and Th2-like human T cells, and only IFN-gamma-producing cells are capable of inducing anti-parasitic effector mechanisms.
Däubener
W
W
Institut für Medizinische Mikrobiologie und Virologie, Heinrich-Heine-Universität, Düsseldorf, Germany.
Mackenzie
C
C
Hadding
U
U
D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D002455:Cell Division; D002460:Cell Line; D002999:Clone Cells; D000939:Epitopes; D005909:Glioblastoma / Q000201:enzymology / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology; D015847:Interleukin-4 / Q000378:metabolism; D018448:Models, Immunological; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology*; D014122:Toxoplasma / Q000276:immunology*; D016781:Toxoplasmosis, Cerebral / Q000276:immunology*; D014366:Tryptophan Oxygenase / Q000378:metabolism
D000953:Antigens, Protozoan; D000939:Epitopes; D015847:Interleukin-4; D007371:Interferon-gamma; D014366:Tryptophan Oxygenase