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

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 whose levels were significantly elevated in the asymptomatic children. Also, using multivariate regression analysis, CTLA-4 was the only marker that could predict parasitaemia load. 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.
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

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