X Zhang1, E Lindwall2, C Gauthier2, J Lyman2, N Spencer3, A Alarakhia2, A Fraser2, S Ing2, M Chen2, T Webb-Detiege4, J Zakem2, W Davis4, Y Sung Choi5, R Quinet4. 1. Institute of Translational Research, Ochsner Clinic Foundation, New Orleans, Louisiana, USA xzhang@ochsner.org. 2. Department of Rheumatology, Ochsner Medical Center, New Orleans, Louisiana, USA. 3. Institute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 4. Department of Rheumatology, Ochsner Medical Center, New Orleans, Louisiana, USA The Univeristy of Queensland, School of Medicine, Ochsner Clinical School, New Orleans, Louisiana, USA. 5. Institute of Translational Research, Ochsner Clinic Foundation, New Orleans, Louisiana, USA.
Abstract
OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies. Recently, a specific highly activated T helper cell subset, follicular helper T (Tfh) cell, has emerged as a key immunoregulator of germinal center (GC) formation and high-affinity antibody production. To identify the pathophysiological role of Tfh cells in SLE patients, we compared the phenotypic and functional properties of circulating Tfh-like cells in lupus patients to GC-Tfh cells, and correlated the percentage of Tfh-like cells with autoantibody production and SLE disease activity. METHODS: Peripheral blood was collected from 29 lupus patients and 25 healthy controls. Tonsils were obtained surgically from non-SLE controls and used as a source of GC-Tfh cells. Tfh cells were defined by their signature surface markers (CXCR5, ICOS, CD57, PD-1 and BTLA) via flow cytometry. IL-21 expression levels from Tfh cells were measured by real-time PCR and intracellular staining. The function of Tfh cells was carried out by co-culture of Tfh cells and autologous B cells in vitro. IgG in the culture supernatant was detected by ELISA. RESULTS: The frequency of circulating Tfh-like cells was significantly increased in SLE patients compared to healthy controls (p < 0.05). The Tfh-like cells not only display similar phenotypes and signature cytokines with GC-Tfh cells, but also are capable of driving B cells to differentiate into IgG-secreting plasma cells in vitro. In addition, the frequency of Tfh-like cells correlated positively with the percentage of circulating plasmablasts, levels of serum anti-dsDNA antibodies and ANA. CONCLUSION: The accumulated circulating Tfh-like cells in lupus patients share phenotypic and functional properties with GC-Tfh cells. Tfh-like cells may serve as perpetuators in the pathogenesis of SLE by enhancing the self-reactive B cell clones to further differentiate into auto antibody-producing plasmablasts, and ultimately cause autoimmunity.
OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies. Recently, a specific highly activated T helper cell subset, follicular helper T (Tfh) cell, has emerged as a key immunoregulator of germinal center (GC) formation and high-affinity antibody production. To identify the pathophysiological role of Tfh cells in SLEpatients, we compared the phenotypic and functional properties of circulating Tfh-like cells in lupuspatients to GC-Tfh cells, and correlated the percentage of Tfh-like cells with autoantibody production and SLE disease activity. METHODS: Peripheral blood was collected from 29 lupuspatients and 25 healthy controls. Tonsils were obtained surgically from non-SLE controls and used as a source of GC-Tfh cells. Tfh cells were defined by their signature surface markers (CXCR5, ICOS, CD57, PD-1 and BTLA) via flow cytometry. IL-21 expression levels from Tfh cells were measured by real-time PCR and intracellular staining. The function of Tfh cells was carried out by co-culture of Tfh cells and autologous B cells in vitro. IgG in the culture supernatant was detected by ELISA. RESULTS: The frequency of circulating Tfh-like cells was significantly increased in SLEpatients compared to healthy controls (p < 0.05). The Tfh-like cells not only display similar phenotypes and signature cytokines with GC-Tfh cells, but also are capable of driving B cells to differentiate into IgG-secreting plasma cells in vitro. In addition, the frequency of Tfh-like cells correlated positively with the percentage of circulating plasmablasts, levels of serum anti-dsDNA antibodies and ANA. CONCLUSION: The accumulated circulating Tfh-like cells in lupuspatients share phenotypic and functional properties with GC-Tfh cells. Tfh-like cells may serve as perpetuators in the pathogenesis of SLE by enhancing the self-reactive B cell clones to further differentiate into auto antibody-producing plasmablasts, and ultimately cause autoimmunity.
Authors: Kateryna Soloviova; Maksym Puliaiev; Mark Haas; Clifton L Dalgard; Brian C Schaefer; Charles S Via Journal: J Immunol Date: 2015-08-28 Impact factor: 5.422
Authors: A Wiener; A Schippers; N Wagner; F Tacke; T Ostendorf; N Honke; K Tenbrock; K Ohl Journal: Clin Exp Immunol Date: 2016-04-18 Impact factor: 4.330