Both CD4(+) FoxP3(+) and CD4(+) FoxP3(-) T cells from patients with B-cell malignancy express cytolytic markers and kill autologous leukaemic B cells in vitro.
2011 (English)In: Immunology, ISSN 0019-2805, E-ISSN 1365-2567, Vol. 133, no 3, 296-306 p.Article in journal (Refereed) Published
P>Cytotoxic CD4+ T cells have been found in patients with chronic lymphocytic leukaemia (CLL) and seem to be involved in the regulation of malignant B cells. The CD4+ T regulatory cells (Tregs) can regulate various immune cells, including B cells, by inducing their apoptosis. Hence, different subgroups of CD4+ T cells may be involved in the regulation of malignant B cells. In this study, the cytotoxic phenotype and function of various CD4+ T-cell subgroups were investigated in patients with B-cell malignancies. Peripheral blood was collected from patients with CLL, various B-cell lymphomas, healthy adult donors, children with precursor B-cell acute lymphoblastic leukaemia (pre-B ALL) and from healthy children. CD4+ T cells (CD3+ CD4+ FoxP3-), Tregs (CD3+ CD4+ CD127low FoxP3+) and CD127high FoxP3+ T cells (CD3+ CD4+ CD127high FoxP3+) were analysed for their expression of the cytolytic markers CD107a and Fas ligand. Patients with CLL had increased CD107a expression on all tested T-cell subgroups compared with healthy donors. Similar results were found in patients with B-cell lymphomas whereas the CD107a expression in children with pre-B ALL was no different from that in healthy controls. Fas ligand expression was similar between patient cells and cells of healthy donors. CD4+ T cells and Tregs from patients with CLL and healthy donors were subsequently purified and cultured in vitro with autologous B cells. Both subgroups lysed B cells and killing was confirmed by granzyme ELISAs. In conclusion, cytotoxic populations of CD4+ T cells, including Tregs, are present in patients with B-cell malignancy and may be an important factor in immune-related disease control.
Place, publisher, year, edition, pages
2011. Vol. 133, no 3, 296-306 p.
B-cell lymphoma, CD107a, chronic lymphocytic leukaemia, Fas ligand, FoxP3, granzyme, precursor B-cell acute lymphoblastic leukaemia
Immunology in the medical area
Research subject Immunology
IdentifiersURN: urn:nbn:se:uu:diva-152265DOI: 10.1111/j.1365-2567.2011.03439.xISI: 000291223300004OAI: oai:DiVA.org:uu-152265DiVA: diva2:413156