title: CD4(+)CD25(+)FoxP3(+) regulatory T cells are increased whilst CD3(+)CD4(-)CD8(-)alphabetaTCR(+) Double Negative T cells are decreased in the peripheral blood of patients with multiple myeloma which correlates with disease burden.
abstract: Increased levels of naturally occurring regulatory T cells (T(Reg) cells) have been found in a variety of solid tumours and haematological malignancies. In multiple myeloma (MM), evidence suggests that T(Reg) cells are increased though controversy exists with regards to their function and no relationship to disease stage and treatment has been demonstrated. Here, we demonstrate significantly elevated levels of functional CD4(+)CD25(+)FoxP3(+) T(Reg) cells in a large cohort of patients with MM as well as monoclonal gammopathy of uncertain significance (MGUS) in comparison to age-matched, healthy controls. The frequency of Double Negative T(Reg) cells was also evaluated, demonstrating that these cells were reduced in patients with MM. Furthermore, a characteristic profile of immunomodulatory cytokines in the peripheral blood and bone marrow of patients with MM and MGUS was demonstrated, compared with healthy controls. This data adds further evidence to the understanding of the role of T(Reg) cell subsets in tumour immunology and the fundamentals of the host/tumour immune conflict.
authors.affiliation: Transplant Immunology Group, Academic Department of Oncology & Haematology, University of Leeds, Leeds, UK.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Feyler
authors.forename: Marie
authors.initials: M
authors.lastname: von Lilienfeld-Toal
authors.forename: Sarah
authors.initials: S
authors.lastname: Jarmin
authors.forename: Lee
authors.initials: L
authors.lastname: Marles
authors.forename: Andy
authors.initials: A
authors.lastname: Rawstron
authors.forename: A J
authors.initials: AJ
authors.lastname: Ashcroft
authors.forename: Roger G
authors.initials: RG
authors.lastname: Owen
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Selby
authors.forename: Gordon
authors.initials: G
authors.lastname: Cook
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017252:CD3 Complex / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D016022:Case-Control Studies; D016207:Cytokines / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology*; D010265:Paraproteinemias / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D018709:Statistics, Nonparametric; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D016693:Receptors, Antigen, T-Cell, alpha-beta