Phenotypic Characterization and in Vitro Response of Lymphocytes of Ghanaian Children with Burkitt’s lymphoma to Plasmodium Falciparum Malaria Antigens

Abstract

It has been shown in epidemiological studies that malaria may play a role in the pathogenesis of endemic Burkitt’s Lymphoma (eBL). The contribution of malaria to the pathogenesis of eBL is believed to be due to the imbalances in the immune regulation during malaria infection. Studies have shown a loss of CTL function due to a shift of the immune responses from Th1 towards Th2 T-cell function during malaria infection. This study sought to investigate the phenotypes of peripheral blood lymphocytes from eBL patients and their responses in vitro to malaria antigens. Lymphocyte subset distributions and activation in the peripheral blood were studied in 22 BL patients and 15 healthy Ghanaian children by flow cytometry. Plasma and supernatant levels of TNF-α and IL-10 were measured by ELISA and compared between the two groups. The results show that lymphocytes from BL patients have significantly low frequencies of CD3+ (p=0.003) and CD8+CD3+ (p=0.013) and both the frequency and the absolute counts of γδ+ T cells (p=0.005 and 0.007 respectively) compared to the controls. The frequency of Vδ1+ γδ+ T cells was significantly higher in the patients compared to the controls (p=0.047). The data also indicates that lymphocytes from BL patients were significantly more activated than those from the controls with regard to the expression of the activation markers, CD95 and HLA-DR by CD3+and γδ + cells. Plasma level of TNF-α was lower (p=0.002) whereas that of IL-10 was higher in BL patients than in controls (p=0.042). Peripheral blood mononuclear cells (PBMC) from BL patients produced significantly less TNF-α compared to the controls when stimulated with Plasmodium falciparum schizonts (p=0.007) and phytohaemagglutinin (PHA) (p=0.050). Similarly, PBMC from BL patients secreted significantly less IL-10 in response to PHA than cells from controls (p=0.016) but with regard to the cells stimulated with P. falciparum schizonts there was no significant difference in secretion of IL-10 between the two groups. Taken together, the data show that there are imbalances in the immune system of BL patients similar to those found in P. falciparum malaria infection suggesting that recurrent P. falciparum infection can be an additive risk factor for the development and persistence of eBL.