Two populations of circulating PD-1hiCD4 T cells with distinct B cell helping capacity are elevated in early rheumatoid arthritis

Fortea-Gordo, P.; Nuño, Laura; Villalba, A.; Peiteado, Diana; Monjo, I.; Sánchez‐Mateos, Paloma; Puig‐Kröger, Amaya; Balsa, Alejandro; Miranda-Carús, María-Eugenia

doi:10.1093/rheumatology/kez169

Cited by 61 publications

(74 citation statements)

References 46 publications

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“…Naïve B cells produce only IgM upon coculture with autologous cTph cells, whereas naïve B cells cocultured with cTfh cells produce classswitched IgG and IgA. 19 Similar findings were reported in CXCR5 − CD4 + T cells in the blood of healthy individuals. 2 Thus, unlike Tfh cells, the target of Tph cells seems to be limited to memory B cells.…”

Section: Similarities Between Tph and Tfh Cellssupporting

confidence: 69%

“…Similar to those of Tfh cells, the B cell helper activities of PD-1 hi CXCR5 − CD4 + T cells are dependent on IL-21 and SLAMF5. 15 However, PD-1 hi CXCR5 − CD4 + T cells express CCR2, CCR5, and CX3CR1, 15,19 chemokine receptors that localize these cells within inflamed tissues enriched with CCL2, CCL5, and CX3CL1. Given their capacity to provide help to B cells and their location in the periphery, PD-1 hi CXCR5 − CD4 + T cells were Tph cells.…”

Section: Tph Cells In Inflamed Ra Jointsmentioning

confidence: 99%

“…These studies showed that key features associated with B helper functions were largely shared. Both subsets express IL-21, CXCL13, PD-1, and TIGIT 15,19,37 and exert B helper activities in a manner largely dependent on IL-21 and SLAMF5. 15 High expression of Maf is integral for IL-21 expression in both Tph and Tfh cells.…”

Section: Similarities Between Tph and Tfh Cellsmentioning

confidence: 99%

“…15 High expression of Maf is integral for IL-21 expression in both Tph and Tfh cells. 29,38 Notably, the frequencies of cTph and cTfh cells are positively correlated in patients with RA and SLE, as well as in healthy subjects, 15,19,29 suggesting that Tph and Tfh cells generally codevelop in our body in both healthy and disease states. This is probably consistent with the fact that Tfh and Tph cells share key cytokines for their differentiation in humans: TGF-β and Activin A [39][40][41] (Fig.…”

Section: Similarities Between Tph and Tfh Cellsmentioning

confidence: 99%

“…15,29 As Bcl-6 is highly associated with the localization of Tfh cells in B cell follicles by upregulating CXCR5 and downregulating CCR7, PSGL1, and EBI2, 45 an increased ratio of Blimp-1 to Bcl-6 likely plays a fundamental role in the peripheral localization of Tph cells, which express the tissue-homing receptors CCR2, CCR5, CXCR3, and CX3CR1. 15,19 Notably, the ability of Tph cells to help naïve B cells is limited, whereas both subsets can provide efficient help to facilitate memory B cells becoming Ig-producing cells. Naïve B cells produce only IgM upon coculture with autologous cTph cells, whereas naïve B cells cocultured with cTfh cells produce classswitched IgG and IgA.…”

Section: Similarities Between Tph and Tfh Cellsmentioning

confidence: 99%

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Shared and distinct roles of T peripheral helper and T follicular helper cells in human diseases

2020

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The interactions of CD4 + T cells and B cells are fundamental for the generation of protective antibody responses, as well as for the development of harmful autoimmune diseases. Recent studies of human tissues and blood samples have established a new subset of CD4 + B helper T cells named peripheral helper T (Tph) cells. Unlike T follicular helper (Tfh) cells, which interact with B cells within lymphoid organs, Tph cells provide help to B cells within inflamed tissues. Tph cells share many B helper-associated functions with Tfh cells and induce B cell differentiation toward antibody-producing cells. The differentiation mechanism is also partly shared between Tph and Tfh cells in humans, and both Tfh and Tph cells can be found within the same tissues, including cancer tissues. However, Tph cells display features distinct from those of Tfh cells, such as the expression of chemokine receptors associated with Tph cell localization within inflamed tissues and a low Bcl-6/Blimp1 ratio. Unlike that of Tfh cells, current evidence shows that the target of Tph cells is limited to memory B cells. In this review, we first summarize recent findings on human Tph cells and discuss how Tph and Tfh cells play shared and distinct roles in human diseases.

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Section: Similarities Between Tph and Tfh Cellssupporting

confidence: 69%

Section: Tph Cells In Inflamed Ra Jointsmentioning

confidence: 99%

Section: Similarities Between Tph and Tfh Cellsmentioning

confidence: 99%

Section: Similarities Between Tph and Tfh Cellsmentioning

confidence: 99%

Section: Similarities Between Tph and Tfh Cellsmentioning

confidence: 99%

See 3 more Smart Citations

Shared and distinct roles of T peripheral helper and T follicular helper cells in human diseases

2020

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Patterns of T‐Cell Phenotypes in Rheumatic Diseases From Single‐Cell Studies of Tissue

Gao

Dunlap

Elahee

et al. 2021

ACR Open Rheumatology

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High‐dimensional analyses of tissue samples from patients with rheumatic diseases are providing increasingly detailed descriptions of the immune cell populations that infiltrate tissues in different rheumatic diseases. Here we review key observations emerging from high‐dimensional analyses of T cells within tissues in different rheumatic diseases, highlighting common themes across diseases as well as distinguishing features. Single‐cell RNA sequencing analyses capture several dimensions of T‐cell states, yet surprisingly, these analyses generally have not demonstrated distinct clusters of paradigmatic T‐cell effector subsets, such as T helper (Th) 1, Th2, and Th17 cells. Rather, global transcriptomics robustly identify both proliferating T cells and regulatory T cells and have also helped to reveal new effector subsets in inflamed tissues, including T peripheral helper cells and granzyme K+ T cells. Further characterization of the T‐cell populations that accumulate within target tissues should enable more precise targeting of biologic therapies and accelerate development of more specific biomarkers to track activity of relevant immune pathways in patients with rheumatic diseases.

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Longitudinal Immune Cell Profiling in Patients With Early Systemic Lupus Erythematosus

Sasaki

Bracero

Keegan

et al. 2022

Arthritis & Rheumatology

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Objectives To investigate the immune cell profiles of patients with systemic lupus erythematosus (SLE), and to identify longitudinal changes in those profiles over time. Methods We employed mass cytometry with 3 different panels of 38–39 markers (an immunophenotyping panel, a T cell/monocyte panel, and a B cell panel) in cryopreserved peripheral blood mononuclear cells (PBMCs) from 9 patients with early SLE, 15 patients with established SLE, and 14 controls without autoimmune disease. We used machine learning–driven clustering, flow self‐organizing maps, and dimensional reduction with t‐distributed stochastic neighbor embedding to identify unique cell populations in early SLE and established SLE. We used mass cytometry data of PBMCs from 19 patients with early rheumatoid arthritis (RA) and 23 controls to compare levels of specific cell populations in early RA and SLE. For the 9 patients with early SLE, longitudinal mass cytometry analysis was applied to PBMCs at enrollment, 6 months after enrollment, and 1 year after enrollment. Serum samples were also assayed for 65 cytokines using Luminex multiplex assay, and associations between cell types and cytokines/chemokines were assessed. Results Levels of peripheral helper T cells, follicular helper T (Tfh) cells, and several Ki‐67+ proliferating subsets (ICOS+Ki‐67+ CD8 T cells, Ki‐67+ regulatory T cells, CD19intermediateKi‐67high plasmablasts, and PU.1highKi‐67high monocytes) were increased in patients with early SLE, with more prominent alterations than were seen in patients with early RA. Longitudinal mass cytometry and multiplex serum cytokine assays of samples from patients with early SLE revealed that levels of Tfh cells and CXCL10 had decreased 1 year after enrollment. Levels of CXCL13 were positively correlated with levels of several of the expanded cell populations in early SLE. Conclusion Two major helper T cell subsets and unique Ki‐67+ proliferating immune cell subsets were expanded in patients in the early phase of SLE, and the immunologic features characteristic of early SLE evolved over time.

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Two populations of circulating PD-1hiCD4 T cells with distinct B cell helping capacity are elevated in early rheumatoid arthritis

Cited by 61 publications

References 46 publications

Shared and distinct roles of T peripheral helper and T follicular helper cells in human diseases

Shared and distinct roles of T peripheral helper and T follicular helper cells in human diseases

Patterns of T‐Cell Phenotypes in Rheumatic Diseases From Single‐Cell Studies of Tissue

Longitudinal Immune Cell Profiling in Patients With Early Systemic Lupus Erythematosus

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