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

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.