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. 2023 Jan 5;13:1068399. doi: 10.3389/fimmu.2022.1068399

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Copyright © 2023 Julé, Lam, Taylor, Hoyt, Wei, Gutierrez-Arcelus, Case, Chandler, Chang, Cohen, Dedeoglu, Halyabar, Hausmann, Hazen, Janssen, Lo, Lo, Meidan, Roberts, Wobma, Son, Sundel, Lee, Sage, Chatila, Nigrovic, Rao and Henderson

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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T peripheral helper cells expressing B cell help factors are enriched in the synovial fluid of autoantibody-positive oligo JIA patients. (A) Representative flow staining of B cell-helper CD4⁺ T cell populations in oligo JIA PB and SF, gated on total CD3⁺CD4⁺ T cells. In each experiment, the PD-1^hi gate was set by evaluating untstimulated PB samples from oligo JIA patients (often paired PB and SF sample from the same patient were used) and controls. This PD-1^hi gate was then applied to SF samples from oligo JIA patients evaluated during the same experiment. (B) Percent of Tph (PD-1^hiCXCR5^-), PD-1^intCXCR5⁺, and Tfh (PD-1⁺CXCR5⁺) cells among CD4⁺ T cells in the SF of oligo JIA patients (ANA^-: n=11, ANA⁺: n=9, blue circles), and in the PB of oligo JIA patients (ANA^-: n=5, ANA⁺: n=5, red circles) and controls (pediatric: n=5, adult: n=6, black circles). (C) Representative flow staining of PD-1^hiCXCL13⁺ T cells in oligo JIA PB and SF, gated on total CD3⁺CD4⁺ T cells. (D) Percent of PD-1^hiCXCL13⁺ and PD-1^hiICOS⁺ cells among CD4⁺ T cells in the SF of oligo JIA patients (ANA^-: n=10-11, ANA⁺: n=9), and in the PB of oligo JIA patients (ANA^-: n=5, ANA⁺: n=5) and controls (pediatric: n=4-5, adult: n=6). (E) Percent of CXCL13⁺ and ICOS⁺ cells among CD4⁺PD-1^intCXCR5^- and Tph subsets in the SF (ANA^-: n=10-11, ANA⁺: n=9) and in the PB (ANA^-: n=5, ANA⁺: n=5) of oligo JIA patients. (F) Representative flow staining of cytokine production in oligo JIA PB and SF, gated on CD4⁺ T cells and subpopulations. (G) Percent of IL-21⁺, IFNγ⁺ and dual IFNγ⁺IL-21⁺ cells among CD4⁺PD-1^intCXCR5^- and Tph subsets in the SF (ANA^-: n=7, ANA⁺: n=7) and in the PB (ANA^-: n=3, ANA⁺: n=5) of oligo JIA patients. Oligo JIA, oligoarticular juvenile idiopathic arthritis; PB, peripheral blood; SF, synovial fluid; pedi, pediatric; ANA, antinuclear antibody; Tph, T peripheral helper cell; Tfh, T follicular helper cell. Summary data on bar graphs are mean ± standard error. P-value <0.05 (*); <0.01 (**), <0.001 (***), <0.0001 (****). Statistical testing: one-way ANOVA followed by multiple t-tests with Turkey correction.