title: Isolation of functional autologous collagen-II specific IL-10 producing Tr1 cell clones from rheumatoid arthritis blood.
abstract: IL-10 producing regulatory type 1 (Tr1) cells represents a subpopulation of CD4+ regulatory cells able to prevent in vitro bystander T-cell proliferation and to inhibit a wide range of inflammatory diseases in mice. Our aim was to evaluate the frequency and function of joint specific Tr1 cells in the peripheral blood of severe Rheumatoid Arthritis (RA) patients. The collagen II protein was chosen to isolate Tr1 cells specific for a joint antigen. We successfully isolated Tr1 clones from 9 out of 11 RA patients. We showed that cells from patients display the same phenotype and surface marker regulation as previously shown for human Tr1 cells, characterized by expression of markers of regulation (FoxP3, CD25) at the activated but not at the resting state. Importantly, cells from patients showed Tr1 cytokine secretion (IL-10 and IFN-γ) and immunosuppressive action on bystander T cell proliferation. Based on these results, we demonstrated that collagen II specific Tr1 cells can be isolated from the blood of severe refractory patients and that these cells are not altered in their phenotype and function.
authors.affiliation: TxCell, SA, Allée de la Nertière, 06560 Valbonne Sophia-Antipolis, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Brun
authors.forename: Virginie
authors.initials: V
authors.lastname: Neveu
authors.forename: Yves Marie
authors.initials: YM
authors.lastname: Pers
authors.forename: Sylvie
authors.initials: S
authors.lastname: Fabre
authors.forename: Brigitte
authors.initials: B
authors.lastname: Quatannens
authors.forename: Hervé
authors.initials: H
authors.lastname: Bastian
authors.forename: Nathalie
authors.initials: N
authors.lastname: Clerget-Chossat
authors.forename: Christian
authors.initials: C
authors.lastname: Jorgensen
authors.forename: Arnaud
authors.initials: A
authors.lastname: Foussat
mesh_terms: D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D048708:Cell Growth Processes / Q000502:physiology; D002999:Clone Cells; D024043:Collagen Type II / Q000097:blood / Q000276:immunology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008297:Male; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*
chemical_list: D024043:Collagen Type II; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D016753:Interleukin-10; D007371:Interferon-gamma