CD4+ T Cell Responses to Toxoplasma gondii 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

Research output: Contribution to journalArticlepeer-review

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 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.

Original languageEnglish
Article number1485
JournalVaccines
Volume11
Issue number9
DOIs
StatePublished - Sep 2023

Keywords

  • CD4 T cells
  • HLA-A*11:01
  • TLR4
  • Toxoplasma gondii
  • vaccine

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