Decreased frequencies of circulating follicular helper T cell counterparts and plasmablasts in ankylosing spondylitis patients Naïve for TNF blockers

PLoS One. 2014 Sep 9;9(9):e107086. doi: 10.1371/journal.pone.0107086. eCollection 2014.

Abstract

Follicular helper T cells (Tfh), localized in lymphoid organs, promote B cell differentiation and function. Circulating CD4 T cells expressing CXCR5, ICOS and/or PD-1 are counterparts of Tfh. Three subpopulations of circulating CD4+CXCR5+ cells have been described: CXCR3+CCR6- (Tfh-Th1), CXCR3-CCR6+ (Tfh-Th17), and CXCR3-CCR6- (Tfh-Th2). Only Tfh-Th17 and Tfh-Th2 function as B cell helpers. Our objective was to study the frequencies of circulating Tfh (cTfh), cTfh subsets and plasmablasts (CD19+CD20-CD27+CD38high cells), and the function of cTfh cells, in patients with Ankylosing Spondylitis (AS). To this end, peripheral blood was drawn from healthy controls (HC) (n = 50), AS patients naïve for TNF blockers (AS/nb) (n = 25) and AS patients treated with TNF blockers (AS/b) (n = 25). The frequencies of cTfh and plasmablasts were determined by flow cytometry. Cocultures of magnetically sorted CD4+CXCR5+ T cells with autologous CD19+CD27- naïve B cells were established from 3 AS/nb patients and 3 HC, and concentrations of IgG, A and M were measured in supernatants. We obseved that AS/nb but not AS/b patients, demonstrated decreased frequencies of circulating CD4+CXCR5+ICOS+PD-1+ cells and plasmablasts, together with a decreased (Tfh-Th17+Tfh-Th2)/Tfh-Th1 ratio. The amounts of IgG and IgA produced in cocultures of CD4+CXCR5+ T cells with CD19+CD27- B cells of AS/nb patients were significantly lower than observed in cocultures established from HC. In summary, AS/nb but not AS/b patients, demonstrate a decreased frequency of cTfh and plasmablasts, and an underrepresentation of cTfh subsets bearing a B helper phenotype. In addition, peripheral blood CD4+CXCR5+ T cells of AS/nb patients showed a decreased capacity to help B cells ex vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • B-Lymphocytes / immunology
  • CD4 Antigens / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • Female
  • Humans
  • Lymphocyte Activation / immunology
  • Male
  • Middle Aged
  • Plasma Cells / immunology*
  • Receptors, CXCR5 / immunology
  • Spondylitis, Ankylosing / immunology*
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Th17 Cells / immunology

Substances

  • CD4 Antigens
  • Receptors, CXCR5

Grants and funding

This work was supported by Fondo de Investigación Sanitaria grant PI-13/00084 from Ministerio de Economía y Competitividad/Instituto de Salud Carlos III (MINECO/ISCIII) (www.isciii.es), by RETICS Program RD12/0009/0012 (Red de Investigación en Inflamación y enfermedades Reumáticas - RIER) from MINECO/ISCIII (www.isciii.es), and by Comunidad Autónoma de Madrid/Fondo Europeo de Desarrollo Regional RAPHYME (http://www.madrimasd.org). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.