ESTABLISHMENT OF T-HELPER TYPE-1-LIKE AND T-HELPER TYPE-2-LIKE HUMAN TOXAPLASMA ANTIGEN-SPECIFIC T-CELL CLONES

As an in vitro model for human cerebral toxoplasmosis, we analysed the interaction between glioblastoma cells, Toxoplasma and Toxoplasma ant igen-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 activate d in glioblastoma cells by T-cell supernatants was the induction of th e tryptophan-degrading enzyme indolamine 2,3-dioxygenase. Enzyme induc tion, as well as the anti-parasitic effect, was blocked by a monoclona l antibody directed against interferon-gamma (IFN-gamma), and the addi tion of L-tryptophan to the cultures completely blocked the anti-paras itic effect induced by T-cell supernatants. The supernatants from two of the 46 established T-cell clones (3A22 and 1A15) were unable to ind uce indolamine 2,3-dioxygenase activity or, as expected, toxoplasmosta sis in glioblastoma cells. We further analysed the supernatants from t hese two clones, and found that they contained large amounts of IL-4 a nd no, or only limited amounts of, IFN-gamma. We therefore conclude th at Toxoplasma-antigen is able to activate T-helper type 1 (Th1)- and T h2-like human T cells, and only IFN-gamma-producing cells are capable of inducing anti-parasitic effector mechanisms.