Open AccessArticle
CD4+ T Cell Responses to Toxoplasma gondii Are a Double-Edged Sword
by
Kamal El Bissati, Paulette A. Krishack, Ying Zhou, Christopher R. Weber, Joseph Lykins, Dragana Jankovic, Karen L. Edelblum, Laura Fraczek, Harshita Grover, Aziz A. Chentoufi, Gurminder Singh, Catherine Reardon, J. P. Dubey, Steve Reed, Jeff Alexander, John Sidney, Alessandro Sette, Nilabh Shastri and Rima McLeod
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Abstract
CD4
+ T cells have been found to play critical roles in the control of both acute and chronic
Toxoplasma infection. Previous studies identified a protective role for the
Toxoplasma CD4
+ T cell-eliciting peptide AS15 (AVEIHRPVPGTAPPS) in C57BL/6J mice. Herein, we found
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CD4
+ T cells have been found to play critical roles in the control of both acute and chronic
Toxoplasma infection. Previous studies identified a protective role for the
Toxoplasma CD4
+ T cell-eliciting peptide AS15 (AVEIHRPVPGTAPPS) in C57BL/6J mice. Herein, we found that immunizing mice with AS15 combined with GLA-SE, a TLR-4 agonist in emulsion adjuvant, can be either helpful in protecting male and female mice at early stages against Type I and Type II
Toxoplasma parasites or harmful (lethal with intestinal, hepatic, and spleen pathology associated with a storm of IL6). Introducing the universal CD4
+ T cell epitope PADRE abrogates the harmful phenotype of AS15. Our findings demonstrate quantitative and qualitative features of an effective
Toxoplasma-specific CD4
+ T cell response that should be considered in testing next-generation vaccines against toxoplasmosis. Our results also are cautionary that individual vaccine constituents can cause severe harm depending on the company they keep.
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