Background/Purpose: Ectopic lymphoid structures are frequently formed in synovial tissues of patients with rheumatoid arthritis (RA). Several reports suggested that CD4 T-cells have a crucial role in pathogenesis of RA. Although Th1 and Th17 cells are key subsets in mouse arthritis models, roles of those subsets in RA patients are still controversial. In this study, we examined an involvement of other T-cell subsets in the pathogenesis of RA. Previous report showed CD4 T-cells in synovial tissues and synovial fluid of RA produced CXCL13 which was crucial for formation of germinal center. We examined whether these cells were related to known Th subset.

Methods: We analyzed CD4 T-cells of RA synovitis by flow cytometry and immunohistofluoresecence.

Results: CD4 T-cells of rheumatoid synovitis produced CXCL13 ex vivo without exogenous stimulation of TCR or cytokines and flow cytometric analyses showed that the CXCL13+ CD4 T-cells were a population independent of IFN-γ⁺ Th1, IL-4⁺ Th2, and IL-17⁺ Th17 cells. Although human follicular helper T-cells, which express CXCR5 as a crucial marker, produce CXCL13, CXCR5 was not expressed in RA synovial CXCL13+ CD4 T-cells. CXCL13+ CD4 T-cells were limited in the local inflamed site but not in blood nor non-inflammatory joints. Moreover, we revealed that TCR stimulation and inflammatory cytokine were important for the maintenance of CXCL13 production and for the induction of CXCL13+ CD4 T-cells from blood CD4+T-cells of healthy volunteer.

Conclusion: Our results showed that CXCL13-producing CD4 T-cells were a newly identified Th subset and distinct from other known Th subsets. The CXCL13+ CD4 T-cells in RA are thought to recruit circulating Tfh cells and B-cells, which express CXCR5, to inflamed joint, to participate in the neogenesis of ectopic lymphoid organ, and to maintain inflammation.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/cxcl13-producing-cd4-t-cells-in-rheumatoid-synovitis-are-a-distinct-subset/