CD8+ T-cell Exhaustion Phenotype in Human Asymptomatic and Ocular Toxoplasmosis

Ocul Immunol Inflamm. 2024 Sep;32(7):1218-1227. doi: 10.1080/09273948.2023.2217906. Epub 2023 Jun 14.

Abstract

This work analyzed exhaustion markers in CD8+ T-cell subpopulations in 21 samples of peripheral blood mononuclear cells (PBMCs) from individuals with ocular toxoplasmosis (n = 9), chronic asymptomatic toxoplasmosis (n = 7), and non-infected people (n = 5) by using RT-qPCR and flow cytometry techniques. The study found that gene expression of PD-1 and CD244, but not LAG-3, was higher in individuals with ocular toxoplasmosis versus individuals with asymptomatic infection or uninfected. Expression of PD1 in CD8+ central memory (CM) cells was higher in nine individuals with toxoplasmosis versus five uninfected individuals (p = .003). After ex vivo stimulation, an inverse correlation was found between the exhaustion markers and quantitative clinical characteristics (lesion size, recurrence index, and number of lesions). A total exhaustion phenotype was found in 55.5% (5/9) of individuals with ocular toxoplasmosis. Our results suggest that the CD8+ exhaustion phenotype is involved in the pathogenesis of ocular toxoplasmosis.

Keywords: CD8+ T cells; PD-1/PDL-1; chronic toxoplasmosis; cytokines; exhaustion markers.

MeSH terms

  • Adult
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • CD8-Positive T-Lymphocytes* / immunology
  • Female
  • Flow Cytometry*
  • Humans
  • Lymphocyte Activation Gene 3 Protein
  • Male
  • Middle Aged
  • Phenotype*
  • Programmed Cell Death 1 Receptor / metabolism
  • Real-Time Polymerase Chain Reaction
  • T-Cell Exhaustion
  • Toxoplasma / immunology
  • Toxoplasmosis, Ocular* / diagnosis
  • Toxoplasmosis, Ocular* / immunology
  • Toxoplasmosis, Ocular* / parasitology
  • Young Adult

Substances

  • Programmed Cell Death 1 Receptor
  • PDCD1 protein, human
  • Antigens, CD
  • Lymphocyte Activation Gene 3 Protein