Beschreibung:
<jats:title>Abstract</jats:title>
<jats:p>Etiological mechanism of eBL remain largely unknown despite long-standing epidemiological link between malaria and EBV co-infection. Age-dependent deficiency in EBV-specific CD8+ T cell-mediated IFN-γ immunosurveillance has been reported in malaria holoendemic exposed children which has been associated with eBL diagnosis. We sought to investigate whether qualitative differences in EBNA-1 specific T cells existed in malaria-exposed children to explain their increased risk for eBL. We conducted a cross-sectional study of healthy children from western Kenya with divergent malaria exposure:Kisumu (holoendemic) and Nandi (hypoendemic) and eBL age-matched patients. T cell effector function was evaluated by multiparameter flow cytometry against T cell lineage markers(CD3,4,8,45RA & CCR7) and functional phenotype (IFN-γ, IL10, IL17 & PD1) to EBNA-1. EBNA-1 specific responses were compared to MSP-1, EBNA2 and EBNA3A. We found significantly higher IFN-γ responses to MSP1 in the eBL & Kisumu compared to Nandi children (p=0.03), in contrast to EBNA1, which were significantly lower in eBL and Kisumu compared to Nandi children (p=0.01). Responses to EBNA2 and EBNA3A did not differ between groups. IFN-γ was generated from CD4 TEM and a heterogeneous combination of CD8 T-cells. PD-1 expressing T-cells were less frequent in eBL patients and highest in Kisumu children.This suggests that the EBNA1-specific deficiencies are due to deletion of T-cell population due to malaria induced exhaustion.</jats:p>