Immunophenotypic Characterization of Lymphocyte Subsets -Expressing Programmed Death-L (Pd-L) in Individuals Exposed to Differential Malaria Transmission Patterns and Endemic Burkitt's Lymphoma
Abstract/ Overview
Repeated..challenge'of the immune system by chronicexposure to high antigen.levels due to persistent infection may lead to development of impaired T-cells that are not effective in . . . . .' \ mediatingimmune functions. Malaria and EBV are two agents that have been implicated in the aetiologyof Burkitts lymphoma. However, the' precise mechanism is unknown but exhaustion/impairementof immune cells has been implicated. Programmed death-I (PD-l) is an . : .. .' immuneinhibitory molecule that negatively regulates activated immune cells.upon interacting withitsIigands.programmed death ligand-I (PD-Ll) and programmed death ligand-Z (PD-L2) resultingin down-regulation of immune responses. Previous studies in murine and primate viral andparasitic diseases have reported the up-regulation of PD-l and sclublePfr-I (sPD-l) but no studieshave reported the expression of PD-l' in individuals from areas.with divergent malaria transmissiofldynamics or in children presentingwith endemic Burkitt'sIymphoma (eBL). A cross-sectional study was carried out in three distinct populations; Kokwet (unstable P. . :." '. . . jalciparumtransmission), Kanyawegi (malaria holoendemic) regions.of Western Kenya and childrenwith' eBL from New Nyanza Provincial General Hospital. PBMC's 'were stained for lymphocyteand PD-l expression markers and data .acquiredusing a four color fiowcytometer. In addition, soluble PD-l in plasma was quantified by Enzyme Linked Immunosorbent Assay (ELISA)in individuals from Kanyawegi, Kokwet andBL. This study reports an increased expressionofPD~l in Kanyawegi compared to Kokwet [(CD4+;p<O.OOOl),(CD8+;p=O.0078), (CD19+;p<O.OOOl)and (CD56+;p<O;OOOl)] and a significant elevated surface expression ofPD1in children with BL [(CD4\ p<O.OOOl), (CD8+;p=O.0418), (CD19+;p<O.OOOl) and (CD56+; . . ". . .. p<O.OOOl)] when compared to age matched children from Kanyawegi and Kokwet.
. . Concentrationof soluble PD-J was significantly increased in BL compared to Kanyawegi and Kokwet(p=O.0074). These data indicate that continuous exposureto malaria upregulates PD-l expression and this upregulation provides. an insight on how malaria modulates immune functionsand in turn may contribute to the pathogenesis of eBL.
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