title: Circulating CXCR5+CD4+helper T cells in systemic lupus erythematosus patients share phenotypic properties with germinal center follicular helper T cells and promote antibody production.
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.
  
  
  CONCLUSIONS
  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.
authors: Institute of Translational Research, Ochsner Clinic Foundation, New Orleans, Louisiana, USA xzhang@ochsner.org.
authors: X
authors: X
authors: Zhang
authors: Department of Rheumatology, Ochsner Medical Center, New Orleans, Louisiana, USA.
authors: E
authors: E
authors: Lindwall
authors: Department of Rheumatology, Ochsner Medical Center, New Orleans, Louisiana, USA.
authors: C
authors: C
authors: Gauthier
authors: Department of Rheumatology, Ochsner Medical Center, New Orleans, Louisiana, USA.
authors: J
authors: J
authors: Lyman
authors: Institute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors: N
authors: N
authors: Spencer
authors: Department of Rheumatology, Ochsner Medical Center, New Orleans, Louisiana, USA.
authors: A
authors: A
authors: Alarakhia
authors: Department of Rheumatology, Ochsner Medical Center, New Orleans, Louisiana, USA.
authors: A
authors: A
authors: Fraser
authors: Department of Rheumatology, Ochsner Medical Center, New Orleans, Louisiana, USA.
authors: S
authors: S
authors: Ing
authors: Department of Rheumatology, Ochsner Medical Center, New Orleans, Louisiana, USA.
authors: M
authors: M
authors: Chen
authors: Department of Rheumatology, Ochsner Medical Center, New Orleans, Louisiana, USA The Univeristy of Queensland, School of Medicine, Ochsner Clinical School, New Orleans, Louisiana, USA.
authors: T
authors: T
authors: Webb-Detiege
authors: Department of Rheumatology, Ochsner Medical Center, New Orleans, Louisiana, USA.
authors: J
authors: J
authors: Zakem
authors: Department of Rheumatology, Ochsner Medical Center, New Orleans, Louisiana, USA The Univeristy of Queensland, School of Medicine, Ochsner Clinical School, New Orleans, Louisiana, USA.
authors: W
authors: W
authors: Davis
authors: Institute of Translational Research, Ochsner Clinic Foundation, New Orleans, Louisiana, USA.
authors: Y Sung
authors: YS
authors: Choi
authors: Department of Rheumatology, Ochsner Medical Center, New Orleans, Louisiana, USA The Univeristy of Queensland, School of Medicine, Ochsner Clinical School, New Orleans, Louisiana, USA.
authors: R
authors: R
authors: Quinet
mesh_terms: D000328:Adult; D000368:Aged; D000917:Antibody Formation; D001323:Autoantibodies / Q000097:blood; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D018858:Germinal Center / Q000276:immunology; D006801:Humans; D007378:Interleukins / Q000097:blood; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D010950:Plasma Cells / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D054380:Receptors, CXCR5 / Q000097:blood* / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D000098546:Interleukin-21
chemical_list: D001323:Autoantibodies; C095085:CXCR5 protein, human; D007378:Interleukins; D054380:Receptors, CXCR5; D000098546:Interleukin-21
keywords: Systemic lupus erythematosus; autoantibody production; follicular helper T cells; germinal center; interleukin 21