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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.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Science for Life Laboratory, SciLifeLab.
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2011 (English)In: Immunology, ISSN 0019-2805, E-ISSN 1365-2567, Vol. 133, no 3, 296-306 p.Article in journal (Refereed) Published
Abstract [en]

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.
Keyword [en]
B-cell lymphoma, CD107a, chronic lymphocytic leukaemia, Fas ligand, FoxP3, granzyme, precursor B-cell acute lymphoblastic leukaemia
National Category
Immunology in the medical area
Research subject
Immunology
Identifiers
URN: urn:nbn:se:uu:diva-152265DOI: 10.1111/j.1365-2567.2011.03439.xISI: 000291223300004OAI: oai:DiVA.org:uu-152265DiVA: diva2:413156
Available from: 2011-04-27 Created: 2011-04-27 Last updated: 2017-12-11

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Mangsbo, SaraTötterman, ThomasFrisk, Per

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