CD4+ Memory Stem T Cells Recognizing Citrullinated Epitopes Are Expanded in Patients With Rheumatoid Arthritis and Sensitive to Tumor Necrosis Factor Blockade

Cianciotti, Beatrice Claudia; Ruggiero, Eliana; Campochiaro, Corrado; Oliveira, Giacomo; Magnani, Zulma; Baldini, Mattia; Doglio, Matteo; Tassara, Michela; Manfredi, Angelo A.; Baldissera, Elena; Ciceri, Fabio; Cieri, Nicoletta; Bonini, Chiara

doi:10.1002/art.41157

Cited by 34 publications

(28 citation statements)

References 39 publications

(55 reference statements)

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“…Recently, a study revealed that CD4 + Tscm cells were expanded in CD4 + T lymphocytes of RA patients and citrullinated vimentin (Vim cit )-specific CD4 + Tscm cells were increased in active RA patients (32). These findings confirmed our current study results in terms of expansion of CD4 + Tscm cells and CD8 + Tscm cells in RA patients even though statistical significance (in case of CD8 + Tscm cells) was not reached in the previous report.…”

Section: Discussionsupporting

confidence: 86%

The pathogenic role of stem cell-like memory T cells in rheumatoid arthritis

Yj¹,

Eh²,

Jw³

et al. 2020

Preprint

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Background: Stem cell-like memory T cells (Tscm) are a subset of memory T cells that have the characteristics of stem cells. The role of Tscm cells in rheumatoid arthritis (RA) is not well characterized.Methods: After measuring percentages of CD4+ and CD8+ Tscm cells within the peripheral blood and synovial mononuclear cell populations in RA and health controls (HCs), we confirmed the stem cell nature of Tscm cells from RA patients. The association of Tscm cells with disease activity was also analyzed. Next, the pathogenicity of Tscm cells was examined in RA patients by assessing T cell activation markers and cytokine secretion after stimulation with IL-6 and anti-CD3/CD28 beads.Finally, the transcriptomes of Tscm cells from RA patients were compared with those from HCs.Results: The percentages of CD4+ and CD8+ Tscm cells among total T cells were significantly higher in RA patients than in HCs. Upon stimulation, Tscm cells from RA patients differentiated into daughter T cell subsets with self-renewal capacity. The percentage of CD4+ Tscm cells correlated with expression of RA disease activity markers. Tscm cells from RA patients were more easily activated by

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Section: Discussionsupporting

confidence: 86%

The pathogenic role of stem cell-like memory T cells in rheumatoid arthritis

Yj¹,

Eh²,

Jw³

et al. 2020

Preprint

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“…For instance, rheumatoid arthritis (RA) patients exhibit memory CD4 + T cells specific for various citrullinated antigens, including citrullinated aggrecan and citrullinated vimentin, which correspond to autoantibodies directed against citrullinated antigens and proteins in these patients [165][166][167]. Furthermore, CD4 + memory cells with a Th17 phenotype and specific for a citrullinated vimentin epitope expanded more significantly in RA patients with active disease and significantly decreased upon anti-TNF treatment [168]. Additionally, memory CD4 + T cells recognizing glycosylated type II collagen peptides have been identified in RA patients [169].…”

Section: Role Of Autoantigen For Memory T Cellsmentioning

confidence: 99%

Memory CD4+ T Cells in Immunity and Autoimmune Diseases

Raphael

Joern

Forsthuber

2020

Cells

121

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CD4 + T helper (Th) cells play central roles in immunity in health and disease. While much is known about the effector function of Th cells in combating pathogens and promoting autoimmune diseases, the roles and biology of memory CD4 + Th cells are complex and less well understood. In human autoimmune diseases such as multiple sclerosis (MS), there is a critical need to better understand the function and biology of memory T cells. In this review article we summarize current concepts in the field of CD4 + T cell memory, including natural history, developmental pathways, subsets, and functions. Furthermore, we discuss advancements in the field of the newly-described CD4 + tissue-resident memory T cells and of CD4 + memory T cells in autoimmune diseases, two major areas of important unresolved questions in need of answering to advance new vaccine design and development of novel treatments for CD4 + T cell-mediated autoimmune diseases.

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“…An advantage of the blood‐tumor overlap analysis is that this analysis can enrich tumor‐associated T‐cell clones in the blood. The blood TCR repertoire contains clones that are not associated with cancer, such as virus‐specific clones 27 and autoreactive clones 28,29 . Thus, it is unclear to what extent the blood TCR repertoire changes represent antitumor T‐cell responses during PD‐1 blockade therapy.…”

Section: Discussionmentioning

confidence: 99%

“…The blood TCR repertoire contains clones that are not associated with cancer, such as virus‐specific clones 27 and autoreactive clones. 28 , 29 Thus, it is unclear to what extent the blood TCR repertoire changes represent antitumor T‐cell responses during PD‐1 blockade therapy. Indeed, the clonality of the blood T‐cell repertoire containing both overlapping and nonoverlapping clones exhibited only weak associations with responses to PD‐1 blockade in this study.…”

Section: Discussionmentioning

confidence: 99%

Greater extent of blood‐tumor TCR repertoire overlap is associated with favorable clinical responses to PD‐1 blockade

et al. 2021

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With the widespread use of programmed death receptor‐1 (PD‐1) blockade therapy, sensitive and specific predictive biomarkers that guide patient selection are urgently needed. T‐cell receptor (TCR) repertoire, which reflects antitumor T‐cell responses based on antigen specificity, is expected as a novel biomarker for PD‐1 blockade therapy. In the present study, the TCR repertoire of eight patients with gastrointestinal cancer treated with anti‐PD‐1 antibody (nivolumab) was analyzed. To analyze the tumor‐associated T‐cell clones in the blood and their mobilization into the tumor, we focused on T‐cell clones that presented in both blood and tumor (blood‐tumor overlapping clones). Responders to PD‐1 blockade tended to exhibit a higher number of overlapping clones in the tumor and a higher total frequency in the blood. Moreover, a higher total frequency of overlapping clones in blood CD8+ T cells before treatment was associated with a favorable clinical response. Collectively, these results suggest the possibility of blood‐tumor TCR repertoire overlap to predict clinical response to PD‐1 blockade and guide patient selection before the treatment.

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CD4+ Memory Stem T Cells Recognizing Citrullinated Epitopes Are Expanded in Patients With Rheumatoid Arthritis and Sensitive to Tumor Necrosis Factor Blockade

Cited by 34 publications

References 39 publications

The pathogenic role of stem cell-like memory T cells in rheumatoid arthritis

The pathogenic role of stem cell-like memory T cells in rheumatoid arthritis

Memory CD4+ T Cells in Immunity and Autoimmune Diseases

Greater extent of blood‐tumor TCR repertoire overlap is associated with favorable clinical responses to PD‐1 blockade

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