CD8 T cells are essential for control of Toxoplasma gondii infection. Once activated they undergo differentiation into short-lived effector and memory precursor effector cells. As effector cells, CD8 T cells exert immune pressure on the parasite via production of inflammatory cytokines and through their cytolytic activity. Once immune control has been established, the parasite encysts and develops into chronic infection regulated by the memory CD8 T-cell population. Several signals are needed for this process to be initiated and for development of fully differentiated memory CD8 T cells. With newly developed tools including CD8 T-cell tetramers and TCR transgenic mice, dissecting the biology behind T. gondii-specific CD8 T-cell responses can now be more effectively addressed. In this paper, we discuss what is known about the signals required for effective T. gondii-specific CD8 T-cell development, their differentiation, and effector function. 1. Introduction Immune protection against many intracellular pathogens including viruses, bacteria, and protozoa is provided by robust CD8 T-cell responses. Na？ve CD8 T cells are found in lymphoid tissues where, after infection, they encounter an antigen-presenting cell (APC) [1]. The APC presents pathogen-derived antigens and provides the appropriate costimulatory signals to the T cell to cause their activation [2, 3]. This activation leads to the proliferation, differentiation, and acquisition of effector functions of the antigen-specific CD8 T cell. Activated antigen-specific CD8 T-cell effector functions include secretion of cytokines IFNγ and TNFα and cytotoxicity, which promote further development of adaptive immunity and control pathogens. Original work by Frenkel revealed that antibodies, when transferred from infected to na？ve hamsters, provided little protection against acute disease in the latter [4]. As such, he adoptively transferred intact or lysed spleen cells from infected animals to na？ve animals then challenged them. He found that only intact cells were able to confer immunity to the recipient animals. Later, using the ts-4 model of infection developed by E. R. Pfefferkorn and L. C. Pfefferkorn [5], Suzuki and Remington [6] further dissected this immunity. Using an antibody depletion strategy with anti-CD4 and anti-CD8, they showed that both CD4 and CD8 T cells were important for control of infection with CD8 T cells playing the dominant role [6]. Further studies by this group using a similar strategy with anti-IFNγ and adoptive transfer of CD8 T cells identified that IFNγ was a major mediator of
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