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Quantitative and qualitative characterization of expanded CD4+ T cell clones in rheumatoid arthritis patients.

Ishigaki K, Shoda H, Kochi Y, Yasui T, Kadono Y, Tanaka S, Fujio K, Yamamoto K - Sci Rep (2015)

Bottom Line: Our in-depth characterization of ECs in RA successfully demonstrated the presence of the specific immunological selection pressure, which determines the phenotype of ECs.Moreover, transcriptome tracking added novel aspects to the underlying sequential immune processes.Our approach may provide new insights into the pathophysiology of RA.

View Article: PubMed Central - PubMed

Affiliation: Department of Allergy and Rheumatology, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.

ABSTRACT
Rheumatoid arthritis (RA) is an autoimmune destructive arthritis associated with CD4(+) T cell-mediated immunity. Although expanded CD4(+) T cell clones (ECs) has already been confirmed, the detailed characteristics of ECs have not been elucidated in RA. Using combination of a single-cell analysis and next-generation sequencing (NGS) in TCR repertoire analysis, we here revealed the detailed nature of ECs by examining peripheral blood (PB) from 5 RA patients and synovium from 1 RA patient. When we intensively investigated the single-cell transcriptome of the most expanded clones in memory CD4(+) T cells (memory-mECs) in RA-PB, senescence-related transcripts were up-regulated, indicating circulating ECs were constantly stimulated. Tracking of the transcriptome shift within the same memory-mECs between PB and the synovium revealed the augmentations in senescence-related gene expression and the up-regulation of synovium-homing chemokine receptors in the synovium. Our in-depth characterization of ECs in RA successfully demonstrated the presence of the specific immunological selection pressure, which determines the phenotype of ECs. Moreover, transcriptome tracking added novel aspects to the underlying sequential immune processes. Our approach may provide new insights into the pathophysiology of RA.

No MeSH data available.


Related in: MedlinePlus

Major memory-ECs were repeatedly detected in RA-PB.Single-cell analysis of PB memory CD4+ T cells from RA1 and RA2 was repeatedly performed with 3-month intervals and the TCR repertoire was analyzed. Each dot and line indicates one clone. Ci.j is the clone ID indicating the j-th expanded major clone in RAi.
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f1: Major memory-ECs were repeatedly detected in RA-PB.Single-cell analysis of PB memory CD4+ T cells from RA1 and RA2 was repeatedly performed with 3-month intervals and the TCR repertoire was analyzed. Each dot and line indicates one clone. Ci.j is the clone ID indicating the j-th expanded major clone in RAi.

Mentions: The existence of ECs has been reported previously in both healthy individuals and RA patients2223. We first examined the persistence of ECs over several months. In two RA patients with stable disease and fixed treatments, the TCR repertoire analysis of PB memory CD4+ T cells was repeatedly performed with 3-month intervals by a single-cell analysis, which is the gold standard method. Since we sorted a maximum of 102 single cells per one sample, we defined ECs in the single-cell analysis as CD4+ T cell clones observed more than once. We detected several identical memory-phenotype ECs (memory-ECs) repeatedly from each patient and confirmed the persistent oligoclonal expansion of major memory-ECs in RA-PB (Fig. 1). Detailed information on the main memory-ECs detected in this pipeline was listed in Table S3. We showed that memory-ECs continuously occupied a significant percentage of memory CD4+ T cells and these results suggested the existence of chronic selection pressure.


Quantitative and qualitative characterization of expanded CD4+ T cell clones in rheumatoid arthritis patients.

Ishigaki K, Shoda H, Kochi Y, Yasui T, Kadono Y, Tanaka S, Fujio K, Yamamoto K - Sci Rep (2015)

Major memory-ECs were repeatedly detected in RA-PB.Single-cell analysis of PB memory CD4+ T cells from RA1 and RA2 was repeatedly performed with 3-month intervals and the TCR repertoire was analyzed. Each dot and line indicates one clone. Ci.j is the clone ID indicating the j-th expanded major clone in RAi.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4542667&req=5

f1: Major memory-ECs were repeatedly detected in RA-PB.Single-cell analysis of PB memory CD4+ T cells from RA1 and RA2 was repeatedly performed with 3-month intervals and the TCR repertoire was analyzed. Each dot and line indicates one clone. Ci.j is the clone ID indicating the j-th expanded major clone in RAi.
Mentions: The existence of ECs has been reported previously in both healthy individuals and RA patients2223. We first examined the persistence of ECs over several months. In two RA patients with stable disease and fixed treatments, the TCR repertoire analysis of PB memory CD4+ T cells was repeatedly performed with 3-month intervals by a single-cell analysis, which is the gold standard method. Since we sorted a maximum of 102 single cells per one sample, we defined ECs in the single-cell analysis as CD4+ T cell clones observed more than once. We detected several identical memory-phenotype ECs (memory-ECs) repeatedly from each patient and confirmed the persistent oligoclonal expansion of major memory-ECs in RA-PB (Fig. 1). Detailed information on the main memory-ECs detected in this pipeline was listed in Table S3. We showed that memory-ECs continuously occupied a significant percentage of memory CD4+ T cells and these results suggested the existence of chronic selection pressure.

Bottom Line: Our in-depth characterization of ECs in RA successfully demonstrated the presence of the specific immunological selection pressure, which determines the phenotype of ECs.Moreover, transcriptome tracking added novel aspects to the underlying sequential immune processes.Our approach may provide new insights into the pathophysiology of RA.

View Article: PubMed Central - PubMed

Affiliation: Department of Allergy and Rheumatology, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.

ABSTRACT
Rheumatoid arthritis (RA) is an autoimmune destructive arthritis associated with CD4(+) T cell-mediated immunity. Although expanded CD4(+) T cell clones (ECs) has already been confirmed, the detailed characteristics of ECs have not been elucidated in RA. Using combination of a single-cell analysis and next-generation sequencing (NGS) in TCR repertoire analysis, we here revealed the detailed nature of ECs by examining peripheral blood (PB) from 5 RA patients and synovium from 1 RA patient. When we intensively investigated the single-cell transcriptome of the most expanded clones in memory CD4(+) T cells (memory-mECs) in RA-PB, senescence-related transcripts were up-regulated, indicating circulating ECs were constantly stimulated. Tracking of the transcriptome shift within the same memory-mECs between PB and the synovium revealed the augmentations in senescence-related gene expression and the up-regulation of synovium-homing chemokine receptors in the synovium. Our in-depth characterization of ECs in RA successfully demonstrated the presence of the specific immunological selection pressure, which determines the phenotype of ECs. Moreover, transcriptome tracking added novel aspects to the underlying sequential immune processes. Our approach may provide new insights into the pathophysiology of RA.

No MeSH data available.


Related in: MedlinePlus