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

<p>Abstract</p> <p>Background</p> <p>The overlap in geographical distribution of <it>Plasmodium falciparum </it>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 <it>P. falciparum </it>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<it>δ</it>1⁺<it>γδ </it>T-cell receptors, is important for maintaining B-cell homeostasis, both in <it>P. falciparum</it>- 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 <it>P. falciparum</it>-exposed Ghanaian children with and without eBL.</p> <p>Methods</p> <p>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-<it>γδ</it>, V<it>δ</it>1, V<it>δ</it>3, V<it>γ</it>9 and B-cells) and acquired on a flow cytometer.</p> <p>Results</p> <p>A reduction in the proportion of CD3⁺cells in eBL patients, due mainly to perturbations among TCR-<it>γδ</it>⁺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.</p> <p>Conclusion</p> <p>Selective changes in numbers and activation status of TCR-<it>γδ</it>⁺cells occurs in Ghanaian children with eBL, a pattern which is similar to <it>P. falciparum</it>-induced changes. The data supports the hypothesis of a regulatory role for V<it>δ</it>1⁺TcR-<it>γδ </it>T-cells in maintaining B-cell homeostasis and provides insights into the pathogenesis of eBL.</p