title: Constitutively altered frequencies of circulating follicullar helper T cell counterparts and their subsets in rheumatoid arthritis.
abstract: BACKGROUND
  Circulating CD4 T cells expressing CXCR5, ICOS and/or PD-1 are counterparts of follicular helper T cells (Tfh). There are three subpopulations of circulating Tfh (cTfh): CXCR5 + CXCR3 + CCR6- (Tfh-Th1), CXCR5 + CXCR3-CCR6- (Tfh-Th2) and CXCR5 + CXCR3-CCR6+ (Tfh-Th17). Our objective was to study the B cell helping capacity of cTfh subsets, and examine their frequency in Rheumatoid Arthritis (RA) patients, together with the frequency of circulating plasmablasts (CD19 + CD20-CD38high).
  
  
  METHODS
  Peripheral blood was drawn from RA patients with active disease (RA-a, DAS28 >2.6) (n = 17), RA in remission (RA-r, DAS28 <2.6) (n = 17) and healthy controls (HC) (n = 34). cTfh and plasmablast frequencies were determined by flow cytometry. Cocultures of sorted CD4 + CXCR5+ T cell subpopulations were established with autologous CD19 + CD27- naïve B cells of HC, and concentrations of IgG, A and M were measured in supernatants.
  
  
  RESULTS
  Isolated Tfh-Th2 and Tfh-Th17 but not Tfh-Th1 cells, induced naïve B cells to secrete IgG and IgA. The frequency of CXCR5+ cells gated for CD4+ T cells was not different among HC, RA-a and RA-r. In contrast, both RA-a and RA-r patients demonstrated an increased frequency of CD4 + CXCR5 + ICOS+ T cells and augmented (%Tfh-Th2 + %Tfh-Th17)/%Tfh-Th1 ratio as compared with HC. In addition, RA-a but not RA-r patients, showed an increased frequency of circulating plasmablasts.
  
  
  CONCLUSIONS
  Both RA-a and RA-r patients demonstrate an increased frequency of cTfh and overrepresentation of cTfh subsets bearing a B cell helper phenotype, suggesting that altered germinal center dynamics play a role in RA pathogenesis. In contrast, only RA-a patients show an increased proportion of circulating plasmablasts.
authors.forename: Irene
authors.initials: I
authors.lastname: Arroyo-Villa
authors.forename: María-Belén
authors.initials: MB
authors.lastname: Bautista-Caro
authors.forename: Alejandro
authors.initials: A
authors.lastname: Balsa
authors.forename: Pilar
authors.initials: P
authors.lastname: Aguado-Acín
authors.forename: María-Gema
authors.initials: MG
authors.lastname: Bonilla-Hernán
authors.forename: Chamaida
authors.initials: C
authors.lastname: Plasencia
authors.forename: Alejandro
authors.initials: A
authors.lastname: Villalba
authors.forename: Laura
authors.initials: L
authors.lastname: Nuño
authors.forename: Amaya
authors.initials: A
authors.lastname: Puig-Kröger
authors.forename: Emilio
authors.initials: E
authors.lastname: Martín-Mola
authors.forename: María-Eugenia
authors.initials: ME
authors.lastname: Miranda-Carús
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D018920:Coculture Techniques; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism*