REGULATION AND FUNCTION OF T-CELL-MEDIATED IMMUNITY DURING TOXOPLASMA-GONDII INFECTION

The intracellular protozoan Toxoplasma gondii is a widespread opportun istic parasite of humans and animals. Normally, T. gondii establishes itself within brain and skeletal muscle tissues, persisting for the li fe of the host. Initiating and sustaining strong T-cell-mediated immun ity is crucial in preventing the emergence of T. gondii as a serious p athogen. The parasite induces high levels of gamma interferon (IFN-gam ma) during initial infection as a result of early T-cell as well as na tural killer (NK) cell activation. Induction of interleukin-12 by macr ophages is a major mechanism driving early IFN-gamma synthesis. The la tter. cytokine, in addition to promoting the differentiation of Th1 ef fectors, is important in macrophage activation and acquisition of micr obicidal functions, such as nitric oxide release. During chronic infec tion, parasite-specific T lymphocytes release high levels of IFN-gamma , which is required to prevent cyst reactivation. T-cell-mediated cyto lytic activity against infected cells, while easily demonstrable, play s a secondary role to inflammatory cytokine production. While part of the clinical manifestations of toxoplasmosis results from direct tissu e destruction by the parasite, inflammatory cytokine-mediated immunopa thologic changes may also contribute to disease progression.