Functional and quantitative analysis of splenic T cell immune responses following oral Toxoplasma gondii infection in mice

Immunity to Toxoplasma gondii is mediated primarily by the host T cell resp onse. Although there is considerable information regarding host immunity fo llowing intraperitoneal infection with tachyzoites, little information is a vailable regarding naturally acquired infection following peroral infection with bradyzoites. In this study, a sequential quantitative analysis of the cell-mediated immune response was performed at me single cell level. To as sess the kinetics of this response and parasitic loads, inbred mice were or ally infected with the 76K strain bradyzoites of T. gondii. Within 24 h of infection, follicular hyperplasia followed by infiltration with histiocytes , macrophages, and apoptotic bodies was observed in the spleens of infected mice. T. gondii were detected from day 1, and counts increased gradually d uring the experimental period. Splenocyte DNA synthesis to antigen and mito gen was severely suppressed at days 7 and 10. The percentages of NK1.1(+) o r delta gamma T cells were increased from day I, whereas CD4(+) and CD8 alp ha(+) T cells were significantly increased after day 7 postinfection. CD25 expression and intracellular IFN-gamma production increased in NK1.1(+) cel ls on day 1 and by all other T cell subsets after day 4. Intracellular IL-4 did not increase until day 7, and ILIO production was increased in all T c ell subsets after day 4. Together, these findings indicate that oral infect ion with T. gondii stimulates a strong cellular immune response that appear s to polarize toward an early Th1 response. However, within 7 days,a strong immune Th2 regulatory response as well as high parasitic loads can be obse rved, with a reduction in lymphoproliferation to mitogen stimulation, incre ased production of IL-4 and IL-10, and evidence of T cell apoptosis in the splenic immune compartment. (C) 1999 Academic Press.