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Gene expression profiling of effector and regulatory T-cells from peripheral blood of rheumatoid arthritis (RA) patients and healthy volunteers-GSE65010

Purpose

Conflicting evidence exists regarding the suppressive capacity of Tregs from the peripheral blood (PB) of patients with rheumatoid arthritis (RA). Our aim was to determine whether Tregs are intrinsically defective in RA using a wide range of read-out assays. Methods: CD3+CD4+CD25+CD127low Tregs from CD45RO+ and CD45RA+ compartments of PB from patients with RA and healthy controls (HC) were analysed for phenotype, cytokine expression profile (ex vivo and after in vitro stimulation), suppression of effector T-cell proliferation and cytokine production, suppression of monocyte-derived cytokine/chemokine production, and gene expression profiling. Results: No differences were observed between patients with RA and HC regarding Treg frequency, ex vivo phenotype (CD4, CD25, CD127, CD39, CD161) or pro-inflammatory cytokine profile (IL-17, IFN-gamma, TNF-alpha). FOXP3 expression was increased in Tregs from RA blood. The ability of Tregs to suppress T-cell proliferation or cytokine (IFN-gamma, TNF-alpha) production upon co-culture with autologous CD45RO+ effector T-cells and monocytes was not significantly different between patients with RA and HC. CD45RO+ Tregs from RA blood showed a slightly impaired ability to suppress production of some cytokines/chemokines by autologous LPS-activated monocytes (IL-1-beta, IL-1Ra, IL-7, CCL3, CCL4), but this was not true for all patients and other cytokines/chemokines (TNF-alpha, IL-6, IL-8, IL-12, IL-15, CCL5) were suppressed in the majority of patients similarly to HC. Finally, gene expression profiling of CD45RA+ or CD45RO+ Tregs from PB revealed no statistically significant differences between patients with RA and HC. Conclusions: Our findings suggest that Tregs isolated from PB of patients with RA are not intrinsically defective.

Hypothesis

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Experimental Design

Sorted regulatory and effector T-cells were isolated from peripheral blood (6 healthy controls and 6 patients with rheumatoid arthritis). Total RNA was isolated and profiled using Affy HG-U133_Plus_2 chips.

Experimental Variables

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Controls

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Methods

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Additional Information

Walter GJ, Fleskens V, Frederiksen KS, Rajasekhar M et al. Phenotypic, Functional, and Gene Expression Profiling of Peripheral CD45RA+ and CD45RO+ CD4+CD25+CD127(low) Treg Cells in Patients With Chronic Rheumatoid Arthritis. Arthritis Rheumatol 2016 Jan;68(1):103-16. PMID: 26314565

Microarray
Affymetrix HG-U133_Plus_2
48 Samples Loaded: 48
Human (Homo sapiens)
Regulatory T Cells
Rheumatoid Arthritis
Sample Set Spreadsheet
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Samples Preview
Sample ID !Sample_title cell type donor disease state
GSM1585731 HC1 Memory T effector purified Memory T effectors HC1 healthy control
GSM1585732 HC2 Naive Treg purified Naive Tregs HC2 healthy control
GSM1585733 HC2 Naive T effector purified Naive T effectors HC2 healthy control
GSM1585734 HC1 Naive Treg purified Naive Tregs HC1 healthy control
GSM1585735 HC1 Naive T effector purified Naive T effectors HC1 healthy control
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Log2 Transformed
Raw Signal
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Sample ID !Sample Title Cell type Donor Disease state
GSM1585731
HC1 Memory T effector
purified Memory T effectors
HC1
healthy control
GSM1585732
HC2 Naive Treg
purified Naive Tregs
HC2
healthy control
GSM1585733
HC2 Naive T effector
purified Naive T effectors
HC2
healthy control
GSM1585734
HC1 Naive Treg
purified Naive Tregs
HC1
healthy control
GSM1585735
HC1 Naive T effector
purified Naive T effectors
HC1
healthy control
GSM1585736
HC1 Memory Treg
purified Memory Tregs
HC1
healthy control
GSM1585737
HC2 Memory Treg
purified Memory Tregs
HC2
healthy control
GSM1585738
HC2 Memory T effector
purified Memory T effectors
HC2
healthy control
GSM1585739
HC3 Naive Treg
purified Naive Tregs
HC3
healthy control
GSM1585740
HC3 Naive T effector
purified Naive T effectors
HC3
healthy control
GSM1585741
HC3 Memory Treg
purified Memory Tregs
HC3
healthy control
GSM1585742
HC3 Memory T effector
purified Memory T effectors
HC3
healthy control
GSM1585743
HC4 Naive Treg
purified Naive Tregs
HC4
healthy control
GSM1585744
HC4 Naive T effector
purified Naive T effectors
HC4
healthy control
GSM1585745
HC4 Memory Treg
purified Memory Tregs
HC4
healthy control
GSM1585746
HC4 Memory T effector
purified Memory T effectors
HC4
healthy control
GSM1585747
HC5 Naive Treg
purified Naive Tregs
HC5
healthy control
GSM1585748
HC5 Naive T effector
purified Naive T effectors
HC5
healthy control
GSM1585749
HC5 Memory Treg
purified Memory Tregs
HC5
healthy control
GSM1585750
HC5 Memory T effector
purified Memory T effectors
HC5
healthy control
GSM1585751
HC6 Naive Treg
purified Naive Tregs
HC6
healthy control
GSM1585752
HC6 Naive T effector
purified Naive T effectors
HC6
healthy control
GSM1585753
HC6 Memory Treg
purified Memory Tregs
HC6
healthy control
GSM1585754
HC6 Memory T effector
purified Memory T effectors
HC6
healthy control
GSM1585755
RA 206 Naive Treg
purified Naive Tregs
RA 206
rheumatoid arthritis
GSM1585756
RA 206 Naive T effector
purified Naive T effectors
RA 206
rheumatoid arthritis
GSM1585757
RA 206 Memory Treg
purified Memory Tregs
RA 206
rheumatoid arthritis
GSM1585758
RA 206 Memory T effector
purified Memory T effectors
RA 206
rheumatoid arthritis
GSM1585759
RA 207 Naive Treg
purified Naive Tregs
RA 207
rheumatoid arthritis
GSM1585760
RA 207 Naive T effector
purified Naive T effectors
RA 207
rheumatoid arthritis
GSM1585761
RA 207 Memory Treg
purified Memory Tregs
RA 207
rheumatoid arthritis
GSM1585762
RA 207 Memory T effector
purified Memory T effectors
RA 207
rheumatoid arthritis
GSM1585763
RA 208 Naive Treg
purified Naive Tregs
RA 208
rheumatoid arthritis
GSM1585764
RA 208 Naive T effector
purified Naive T effectors
RA 208
rheumatoid arthritis
GSM1585765
RA 208 Memory Treg
purified Memory Tregs
RA 208
rheumatoid arthritis
GSM1585766
RA 208 Memory T effector
purified Memory T effectors
RA 208
rheumatoid arthritis
GSM1585767
RA 209 Naive Treg
purified Naive Tregs
RA 209
rheumatoid arthritis
GSM1585768
RA 209 Naive T effector
purified Naive T effectors
RA 209
rheumatoid arthritis
GSM1585769
RA 209 Memory Treg
purified Memory Tregs
RA 209
rheumatoid arthritis
GSM1585770
RA 209 Memory T effector
purified Memory T effectors
RA 209
rheumatoid arthritis
GSM1585771
RA 211 Naive Treg
purified Naive Tregs
RA 211
rheumatoid arthritis
GSM1585772
RA 211 Naive T effector
purified Naive T effectors
RA 211
rheumatoid arthritis
GSM1585773
RA 211 Memory Treg
purified Memory Tregs
RA 211
rheumatoid arthritis
GSM1585774
RA 211 Memory T effector
purified Memory T effectors
RA 211
rheumatoid arthritis
GSM1585775
RA 212 Naive Treg
purified Naive Tregs
RA 212
rheumatoid arthritis
GSM1585776
RA 212 Naive T effector
purified Naive T effectors
RA 212
rheumatoid arthritis
GSM1585777
RA 212 Memory Treg
purified Memory Tregs
RA 212
rheumatoid arthritis
GSM1585778
RA 212 Memory T effector
purified Memory T effectors
RA 212
rheumatoid arthritis

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