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

Abstract

BackgroundThe 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 Vδ1+ γδ 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.MethodsVenous 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-γδ, Vδ1, Vδ3, Vγ9 and B-cells) and acquired on a flow cytometer.ResultsA reduction in the proportion of CD3+ cells in eBL patients, due mainly to perturbations among TCR-γδ+ 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.ConclusionSelective changes in numbers and activation status of TCR-γδ+ 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 Vδ1+ TcR-γδ T-cells in maintaining B-cell homeostasis and provides insights into the pathogenesis of eBL.

Histological characteristics of 21 Papua New Guinean children with high‐grade B‐cell lymphoma, which is frequently associated with EBV infection

“…With respect to the pathogenic mechanism of eBL, previous studies have suggested that control of EBV‐infected B‐cell multiplication can fail under certain circumstances, and that EBV consequently plays the role of a co‐factor in the development of BL 2 . It has been considered that there are certain differences in the c‐MYC breakpoint translocation between eBL (or EBV‐positive BL) and sBL (or EBV‐negative BL); 14,19 but we could not perform genetic analysis of the Papua New Guinean specimens in the present study.…”

“…It has been considered that there are certain differences in the c‐MYC breakpoint translocation between eBL (or EBV‐positive BL) and sBL (or EBV‐negative BL); 14,19 but we could not perform genetic analysis of the Papua New Guinean specimens in the present study. In addition, epidemiological evidence suggests that malaria is a risk factor for eBL, because the geographical distributions of malaria and eBL strikingly overlap, and malaria causes temporary immunosuppression and marked polyclonal B‐cell activation 2,15,20,21 …”

“…EBV is a ubiquitous herpes virus that was initially found in cultures of BL, which are B‐cell lymphomas that affect children in central Africa 1 . With regard to the relationship between EBV infection and lymphomas, it is known that EBV can infect and immortalize B cells 2 . In a study on pediatric patients, Peh et al .…”

Gamma Delta T Cell Therapy for Cancer: It Is Good to be Local

“…However, Vδ3 cells are relatively rare in blood and conditions for expanding these cells ex vivo are poorly defined. Cellular recognition of EBV- or CMV-infected cells has also been documented for Vδ1 or Vδ2 cells ( 42 , 46 ) and in rare cases, the Vδ5+ subset also recognized herpesvirus-infected cells ( 44 ).…”

Dual Face of Vγ9Vδ2-T Cells in Tumor Immunology: Anti- versus Pro-Tumoral Activities

“…CC and CXC chemokines are produced by most tumor cells, such as breast, cervix, pancreatic, and ovarian tumor cells ( 57 ). To provide optimal protection against tumor cells, the cytotoxic Vγ9Vδ2-T cells must migrate from the bloodstream to tumor site ( 33 , 100 , 101 ) (Figure 2 ). Unlike Vδ1 γδ-T cells which express lymph node homing chemokine receptor C-C chemokine receptor 7 (CCR7), the circulating Vγ9Vδ2-T cells preferentially express inflammatory homing chemokine receptor CCR5, which can mediate the migration of Vγ9Vδ2-T cells to CCR5 ligands that are expressed in tumor cells ( 20 , 102 ).…”