Constitutively altered frequencies of circulating follicullar helper T cell counterparts and their subsets in rheumatoid arthritis

摘要

Introduction 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- na?ve 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 na?ve 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. Conclusion 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.