Selective activation of TCR-γδ+ cells in endemic Burkitt's lymphoma

Background: The overlap in geographical distribution of Plasmodium falciparum malaria and endemic Burkitt's lymphoma (eBL) - an aggressive Epstein-Barr virus (EBV)- associated B-cell tumour occurring almost exclusively in the tropics - strongly suggests a link between the two diseases. It is suspected that the polyclonal B-cell activation in P. falciparum malaria may precipitate a breakdown in homeostatic T-cell control of EBV-immortalized B-cell proliferation. Previous studies have suggested that a particular T-cell subset, characterized by expression of V delta l(+) gamma delta T-cell receptors, is important for maintaining B-cell homeostasis, both in P. falciparum-exposed populations and in individuals subject to polyclonal B-cell activation of other aetiology. The objective of the present study was, therefore, to characterize lymphocyte phenotypes and to investigate possible differences in T-cell subset composition and activation status in P. falciparum-exposed Ghanaian children with and without eBL. Methods: Venous blood samples in heparin from 21 eBL patients ( mean age: 7.0 years; range: 3-11 years), referred to the Burkitt's Tumour Centre at Korle-Bu Teaching Hospital, Accra and 15 healthy, age and sex matched children, were stained with fluorescein isothiocyanate ( FITC)-, phycoerythrin ( PE)-, R-phycoerythrin (RPE)- and RPE-Cy5-conjugated antibodies (CD3, CD4, CD8, CD25, CD69, CD95, HLA-DR, TCR-gamma delta, V delta 1, V delta 3, V gamma 9 and B-cells) and acquired on a flow cytometer. Results: A reduction in the proportion of CD3(+) cells in eBL patients, due mainly to perturbations among TCR-gamma delta(+) cells was observed. In contrast, the proportions of CD4(+) or CD8(+) cells were relatively unaffected, as were the mean numbers of peripheral blood mononuclear cells. Conclusion: Selective changes in numbers and activation status of TCR-gamma delta(+) cells occurs in Ghanaian children with eBL, a pattern which is similar to P. falciparum-induced changes. The data supports the hypothesis of a regulatory role for V delta I+ TcR-gamma delta T-cells in maintaining B-cell homeostasis and provides insights into the pathogenesis of eBL.