title: 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.
abstract: 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(+) CD127(low) FoxP3(+)) and CD127(high) FoxP3(+) T cells (CD3(+) CD4(+) CD127(high) 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.
authors.affiliation: Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Sweden.
authors.forename: Camilla A
authors.initials: CA
authors.lastname: Lindqvist
authors.forename: Lisa H
authors.initials: LH
authors.lastname: Christiansson
authors.forename: Ingrid
authors.initials: I
authors.lastname: Thörn
authors.forename: Sara
authors.initials: S
authors.lastname: Mangsbo
authors.forename: Gabriella
authors.initials: G
authors.lastname: Paul-Wetterberg
authors.forename: Christer
authors.initials: C
authors.lastname: Sundström
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Tötterman
authors.forename: Bengt
authors.initials: B
authors.lastname: Simonsson
authors.forename: Gunilla
authors.initials: G
authors.lastname: Enblad
authors.forename: Per
authors.initials: P
authors.lastname: Frisk
authors.forename: Ulla
authors.initials: U
authors.lastname: Olsson-Strömberg
authors.forename: Angelica S I
authors.initials: AS
authors.lastname: Loskog
mesh_terms: D001402:B-Lymphocytes / Q000166:cytology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016923:Cell Death; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D051858:Forkhead Transcription Factors / Q000276:immunology*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000502:physiology
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors