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I. Blader, E. Charles; Adaptive Immune Responses Against Toxoplasma gondii in the Eye. Invest. Ophthalmol. Vis. Sci. 2008;49(13):825.
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In the retina and other tissues, chronic Toxoplasma infections sporadically reactivate. In most cases, the host can mount efficient immune responses against these reactivated infections to prevent tissue damage and vision loss. How adaptive immune responses function against Toxoplasma in an immune-privileged tissue like the retina is unknown. A major obstacle to addressing this question has been the need to either genetically or pharmacologically immune suppress a mouse in order for chronic infections to reactivate. These conditions, however, abrogate the ability for us to study adaptive immune responses. The goal of this study was to establish a murine model to assess adaptive immune responses in the retinas of otherwise healthy immune competent mice.
C57BL/6 mice were vaccinated by infecting mice with cpsII attenuated Toxoplasma strain parasites every 14 days for 4 weeks. Then, the vaccinated or unvaccinated mice were intravitreally infected with 100 parasites and 8 days later the eyes were harvested and H&E stained. The stained sections were then analyzed in a blinded manner and assigned histopathological scores. Next, we compared by flow cytometry T-cell, monocyte, and neutrophil recruitment.
Our data show that in contrast to immunologically naïve mice the vaccinated mice were significantly protected from developing significant Toxoplasma-induced retinal damage. Consistent with this protection, we find a significant increase in numbers of T-cells and 75% of which were CD4+. This is in contrast to infected brains where 75% of the infiltrating T-cells are CD8+. Besides T-cells neutrophils and monocytes were the other leukocytes detected in parasite-infected retinas.
Intravitreally infected mice that were previously systemically protected and from developing severe retinal damage. In comparison to naïve mice, we find a significant increase in the numbers of T-cells in the eyes of the vaccinated mice. Given the clear requirement for cell-mediated immunity against Toxoplasma gondii, these data indicate that we have developed a murine model to analyze anti-Toxoplasma adaptive immune responses in the retina of otherwise healthy mice.
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