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Quantitative and qualitative characterization of expanded CD4+ T cell clones in
rheumatoid arthritis patients
#MMPMID26245356
Ishigaki K
; Shoda H
; Kochi Y
; Yasui T
; Kadono Y
; Tanaka S
; Fujio K
; Yamamoto K
Sci Rep
2015[Aug]; 5
(?): 12937
PMID26245356
show ga
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.
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