Background RA is an autoimmune condition characterized by chronic joint inflammation. Tfh cells, a recently described Th subset localized in lymphoid organs, help B cell differentiation and function. Circulating central memory CD4 T cells expressing CXCR5 can be subdivided into three different subpopulations based on the combined expression of surface CXCR5 with or without CCR6 and/or CXCR3: CXCR5+CXCR3+CCR6- (Tfh-Th1), CXCR5+CXCR3-CCR6+ (Tfh-Th17) and CXCR5+CXCR3-CCR6- (Tfh-Th2). Only Tfh-Th17 and Tfh-Th2 cells have been demonstrated to display functional properties of Tfh cells; in contrast Tfh-Th1 cells are unable to provide B cell help. An altered proportion of these subpopulations has been associated with autoimmune diseases.
Objectives To study the frequency of circulating CXCR5+CD4+ T cell subsets together with the frequency of circulating plasmablasts (CD19+CD20-CD27+CD38high B cells) in patients with RA.
Methods Peripheral blood was drawn from healthy controls (n=27) and RA patients (n=27). After isolation by Ficoll-Hypaque gradient, PBMCs were stained with antibodies to CD3, CD4, CXCR5, CCR6, CXCR3, CD19, CD20, CD27, and CD38, and examined by flow cytometry. The percentages of CXCR5+CXCR3+CCR6- (Tfh-Th1), CXCR5+CXCR3-CCR6+ (Tfh-Th17) and CXCR5+CXCR3-CCR6- (Tfh/Th2) cells were calculated after gating for CD3, CD4 and CXCR5+. The percentage of CD20-CD38high cells was calculated after gating for CD19+ and CD27+.
Results The frequency of circulating CXCR5+ cells gated for CD4+ T cells was not different among the studied groups. In contrast, in RA patients, the frequency of Tfh-Th1 cells was significantly decreased and the frequency of Tfh-Th17 and Tfh-Th2 cells was significantly increased as compared with controls. Subsequently, the ratio (Tfh-Th17+Tfh-Th2)/Tfh-Th1 was increased in RA patients. That is, RA patients demonstrate a higher proportion of Tfh cells bearing a phenotype associated with B cell helping capacity. At the same time, the frequency of circulating plasmablasts was increased in RA patients as compared with controls. Interestingly, there was a significantly positive correlation between the percentage of circulating plasmablasts and the ratio (Tfh-Th17+Tfh-Th2)/Tfh-Th1, together with a significantly negative correlation between the percentage of circulating plasmablasts and the percentage of circulating Tfh-Th1 cells.
Conclusions RA patients demonstrate altered proportions of circulating Tfh subpopulations, with overrepresentation of subsets bearing a phenotype associated with B cell helping capacity. At the same time, an increased proportion of circulating plasmablasts is apparent in RA patients.
Disclosure of Interest None Declared
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