IL-21 Is Required for Optimal Antibody Production and T Cell Responses during Chronic Toxoplasma gondii Infection

Previous studies have indicated that Il21r^−/− mice chronically infected with Toxoplasma gondii display a defect in serum IgG; however, the basis for this antibody defect was not defined and questions remain about the role of IL-21 in promoting the production of IL-10, which is required to limit infection-induced pathology during toxoplasmosis. Therefore, Il21^−/− mice were challenged with T. gondii to determine whether IL-21 impacts the parasite-specific CD8⁺ T cell response, its contribution to thymus-dependent antibody production after infection, and balance between protective and pathogenic responses. Whereas IL-21 has been implicated in the differentiation of IL-10 producing CD4⁺ T cells no immune-mediated pathology was evident in Il21^−/− mice during the acute response, nor was there a defect in the development of this population in chronically infected Il21^−/− mice. However, Il21^−/− mice displayed a defect in IgG production after infection that correlated with a decrease in GC B cell numbers, the CD4⁺ and CD8⁺ T cell numbers in the brain were reduced over the course of the chronic infection leading to a decrease in total IFN-γ production and an increase in parasite numbers associated with susceptibility to toxoplasmic encephalitis. Together, these results identify a key role for IL-21 in shaping the humoral and cellular response to T. gondii, but indicate that IL-21 has a limited role in regulating immunopathology. [ABSTRACT FROM AUTHOR]