title: IL-21 is required for optimal antibody production and T cell responses during chronic Toxoplasma gondii infection.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America. jstumhofer@uams.edu
authors.forename: Jason S
authors.initials: JS
authors.lastname: Stumhofer
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Silver
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Hunter
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis* / Q000276:immunology; D001921:Brain / Q000469:parasitology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002470:Cell Survival; D002908:Chronic Disease; D004660:Encephalitis / Q000469:parasitology; D005786:Gene Expression Regulation / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D007378:Interleukins / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D053655:Receptors, Interleukin-21 / Q000378:metabolism; D013045:Species Specificity; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D014122:Toxoplasma / Q000276:immunology* / Q000502:physiology; D014123:Toxoplasmosis / Q000276:immunology*; D000098546:Interleukin-21
chemical_list: D000913:Antibodies, Protozoan; D007378:Interleukins; D053655:Receptors, Interleukin-21; D016753:Interleukin-10; D007371:Interferon-gamma; D000098546:Interleukin-21