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 o f endemic Burkitt’s Lymphoma (eBL). The contribution o f m alaria to the

pathogenesis o f eBL is believed to be due to the imbalances in the immune regulation

during malaria infection. Studies have shown a loss o f CTL function due to a shift o f the

immune responses from T h l towards Th2 T-cell function during malaria infection. This

study sought to investigate the phenotypes o f 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 o f TN F-a 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 o f CD3+ (p=0.003) and

CD8+CD3+ (p=0.013) and both the frequency and the absolute counts o f y8+ T cells

(p=0.005 and 0.007 respectively) compared to the controls. The frequency o f V51+ yd+ 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 o f the activation markers, CD95 and

HLA-DR by CD3T and y5+cells. Plasma level o f TNF-a was lower (p=0.002) whereas

that o f 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-a

compared to the controls when stimulated with Plasmodium fa lc ip a rum 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. fa lc ip a rum schizonts there was

no significant difference in secretion o f IL-10 between the two groups. Taken together,

the data show that there are imbalances in the immune system o f BL patients similar to

those found in P. fa lc ip a rum malaria infection suggesting that recurrent P. falciparum

infection can be an additive risk factor for the development and persistence o f eBL.