Cytotoxic Signature and IFN‐γ Production Dominate CD4+ T‐Cell Response During Human Toxoplasmosis

• DOI: 10.1111/imm.13912
• Publication Date: 2025-03-12T04:17:36Z
• Authors: Priscilla Miranda...; Gregório Guilherm...; Inga Rimkute; Luara Isabela dos...; Thomas Liechti; Ana Paula Marino; Isabela Natália P...; Daniel Vitor Vasc...; Olindo Assis Mart...; Ricardo Tostes Ga...; Mario Roederer; Alan Sher; Andréa Teixeira‐C...; Dragana Jankovic; Lis Ribeiro do Va...

ABSTRACT Toxoplasma gondii is a highly versatile parasite that infects most warm‐blooded animals and major cause of retinochoroiditis uveitis in humans. The pathophysiology these conditions remains poorly understood. Both virulence host inflammatory response contribute to the development ocular disease. While CD4 + T cells play critical role resistance infection, their kinetics effector functions, as well contribution clinical outcome including involvement, remain To address this question, we investigated immune during acute convalescent toxoplasmosis stratified patients further based on presence or absence We found T. infection leads decreased increased proportions central memory cells, respectively. Applying unsupervised analysis, distinct T‐cell subsets were determined. Among 50 clusters, 10 produced cytotoxic proteins (granzyme B perforin) one cytokines upon antigen‐specific stimulation. observed five clusters out different disease between ‐infected with without lesions. Interestingly, three displayed signature indicating possible involvement immunopathology. Taken together, our results reveal not only develop Th1 cytokine profile, but also acquire previously unappreciated capacity/function. These results, while underscoring complexity , suggest specific may be involved pathology provide targets for therapeutic intervention.