Phenotypic Evidence of T Cell Exhaustion and Senescence During Symptomatic Plasmodium falciparum Malaria

Front Immunol. 2019 Jun 18:10:1345. doi: 10.3389/fimmu.2019.01345. eCollection 2019.

Abstract

T cells play significant roles during Plasmodium falciparum infections. Their regulation of the immune response in symptomatic children with malaria has been deemed necessary to prevent immune associated pathology. In this study, we phenotypically characterized the expression of T cell inhibitory(PD-1, CTLA-4) and senescent markers (CD28(-), CD57) from children with symptomatic malaria, asymptomatic malaria and healthy controls using flow cytometry. We observed increased expression of T cell exhaustion and senescence markers in the symptomatic children compared to the asymptomatic and healthy controls. T cell senescence markers were more highly expressed on CD8 T cells than on CD4 T cells. Asymptomatically infected children had comparable levels of these markers with healthy controls except for CD8+ PD-1+ T cells which were significantly elevated in the asymptomatic children. Also, using multivariate regression analysis, CTLA-4 was the only marker that could predict parasitaemia level. The results suggest that the upregulation of immune exhaustion and senescence markers during symptomatic malaria may affect the effector function of T cells leading to inefficient clearance of parasites, hence the inability to develop sterile immunity to malaria.

Keywords: CD57; CTLA-4; PD-1; Plasmodium falciparum; T-cell; exhaustion; immune senescence; malaria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asymptomatic Infections
  • CD28 Antigens / genetics
  • CD28 Antigens / immunology
  • CD28 Antigens / metabolism
  • CD57 Antigens / genetics
  • CD57 Antigens / immunology
  • CD57 Antigens / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / parasitology
  • CTLA-4 Antigen / genetics
  • CTLA-4 Antigen / immunology
  • CTLA-4 Antigen / metabolism
  • Cells, Cultured
  • Cellular Senescence / genetics
  • Cellular Senescence / immunology*
  • Child
  • Child, Preschool
  • Female
  • Gene Expression Profiling / methods
  • Humans
  • Immunophenotyping
  • Malaria, Falciparum / immunology*
  • Malaria, Falciparum / parasitology
  • Male
  • Parasitemia / genetics
  • Parasitemia / immunology
  • Parasitemia / metabolism
  • Plasmodium falciparum / immunology*
  • Plasmodium falciparum / physiology
  • Programmed Cell Death 1 Receptor / genetics
  • Programmed Cell Death 1 Receptor / immunology
  • Programmed Cell Death 1 Receptor / metabolism

Substances

  • CD28 Antigens
  • CD57 Antigens
  • CTLA-4 Antigen
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor