Immunophenotypic characterization of B and T cells in children during acute and recovery phases of malaria.

Abstract

Studies of the epidemiology and immune parameters in individuals at risk for African Burkitt's lymphoma (ABL) development has provided strong support for the involvement of malaria in African Burkitt's lymphoma pathogenesis. However, there is still a fundamental lack of understanding of the mechanisms by which malaria infection interacts with the host immune system, Epstein Barr Virus (EBV) infection and cellular oncogene deregulation to promote development of malignant B-cell clones. This study was designed to answer some of these questions. Using flow cytofluorometric techniques (FCF), the T and B-cell surface markers CD3 (all T cells), CD4 (helper T cells), CD8 (cytotoxic T cells), (all B cells), CD27 (memory B cells), CD10 (Burkitt's lymphoma tumor cell marker), CD23 (activated B cells), CD38 (plasmablast B cells) and IgD (naive B cells) were quantified in 15 children aged 2-6 years during episodes of acute clinical malaria, post recovery and six healthy age matched controls who are parasitaemic but asymptomatic by gating on CD45 for lymphocytes, CD3+ for T cells and CD19+ for B cells. Wilcoxon signed rank test was used to test statistical significance for two related samples and Mann-Whitney test for two unrelated samples. The results of this study showed that the expression of CD3+T cells were statistically comparable in the three groups. Similarly, the frequencies of CD4+ T cells were statistically comparable within the three groups. The frequencies of CD8+ T cells however was significantly higher in the control compared to children experiencing an episode of acute clinical malaria (P=0.029) and post recovery (P=0.023), although during those two clinical time points, the frequencies of CD8+T cells expression were comparable (P=0.7764). The expressions of CD19+B cells were statistically higher during post-recovery compared to during acute clinical malaria (P=0.0356) but its frequencies were comparable between the controls and post-recovery (P=0.718) and during acute clinical malaria compared to the controls (P=0.112). The frequency of CD19+CD38+ was significantly higher during acute clinical malaria compared to post-recovery (P=0.0110). The frequency of CD19+CD27+ was compared during acute clinical malaria and post recovery (P=0.1771). The frequency of the CD19+CD10+ subsets was significantly higher in children during post-recovery compared to during acute clinical malaria (P=0.0132). The frequency of CD19+CD23+ was significantly higher in children during post-recovery compared to during acute clinical malaria (P=0.0029). The frequency of IgD+CD38+ was significantly higher in children in children during post-recovery compared to during acute clinical malaria (P=0.0132). The frequency of IgD-CD38- was significantly higher in children during acute clinical malaria compared to post-recovery compared (P=0.0500). The frequency of CD38+CD23+ was significantly higher in children during post-recovery compared to during acute clinical malaria (P=0.0110). The frequency of CD38-CD23- was significantly higher in children during acute clinical malaria compared to post-recovery compared (P=0.0110). These results suggested that acute episodes of P.falciparum malaria cause perturbation in the critical arm of the immune system responsible for immunesurvielance of persistent EBV infections and also alterations in B cell phenotype and differentiation, suggesting that malaria is not just increasing B cell numbers but also shifting the B cell pool. Therefore studies focusing on the interaction of these two co-factors would provide clues as to the mechanism by which these co-factors increase the risk of ABL.