CD4<sup>+</sup> T Cell Responses to <i>Toxoplasma gondii</i> Are a Double-Edged Sword
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,
Rima McLeod
Affiliations
Kamal El Bissati
Institute of Molecular Engineering, University of Chicago Medical Center, Chicago, IL 60637, USA
Paulette A. Krishack
Department of Pathology, University of Chicago, Chicago, IL 60637, USA
Ying Zhou
Department of Ophthalmology and Visual Sciences, University of Chicago, Chicago, IL 60637, USA
Christopher R. Weber
Department of Pathology, University of Chicago, Chicago, IL 60637, USA
Joseph Lykins
Department of Ophthalmology and Visual Sciences, University of Chicago, Chicago, IL 60637, USA
Dragana Jankovic
Immunoparasitology Unit, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Karen L. Edelblum
Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Laura Fraczek
Department of Ophthalmology and Visual Sciences, University of Chicago, Chicago, IL 60637, USA
Harshita Grover
Division of Immunology and Pathogenesis, Department of Molecular and Cellular Biology, University of California, Berkeley, CA 94720, USA
Aziz A. Chentoufi
Department of Medical Microbiology, Faculty of Health Sciences, University of Pretoria, Pretoria 0028, South Africa
Gurminder Singh
Department of Pathology, University of Chicago, Chicago, IL 60637, USA
Catherine Reardon
Department of Pathology, University of Chicago, Chicago, IL 60637, USA
J. P. Dubey
Animal Parasitic Diseases Laboratory, Beltsville Agricultural Research Center, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD 20705, USA
Steve Reed
Infectious Diseases Research Institute, 1616 Eastlake Ave E #400, Seattle, WA 98102, USA
Jeff Alexander
PaxVax, 3985-A Sorrento Valley Blvd, San Diego, CA 92121, USA
John Sidney
La Jolla Institute of Allergy and Immunology, 9420 Athena Cir, La Jolla, CA 92037, USA
Alessandro Sette
La Jolla Institute of Allergy and Immunology, 9420 Athena Cir, La Jolla, CA 92037, USA
Nilabh Shastri
Division of Immunology and Pathogenesis, Department of Molecular and Cellular Biology, University of California, Berkeley, CA 94720, USA
Rima McLeod
Department of Ophthalmology and Visual Sciences, University of Chicago, Chicago, IL 60637, USA
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.
