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Circulating CD4+CD161+ T lymphocytes are increased in seropositive arthralgia patients but decreased in patients with newly diagnosed rheumatoid arthritis.

Chalan P, Kroesen BJ, van der Geest KS, Huitema MG, Abdulahad WH, Bijzet J, Brouwer E, Boots AM - PLoS ONE (2013)

Bottom Line: Precursor Th17 lineage cells bearing CD161 were found to be increased in seropositive arthralgia patients.The decrease in CD4+CD161+ T-cells correlated inversely with C-reactive protein and with the 66 swollen joint count.In addition, synovial fluid from late-stage disease was found to be enriched for CD4+CD161+ T-cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, Groningen, The Netherlands ; Groningen research initiative on healthy ageing and immune longevity (GRAIL), Groningen, The Netherlands.

ABSTRACT
Improved understanding of the immune events discriminating between seropositive arthralgia and clinical synovitis is of key importance in rheumatology research. Ample evidence suggests a role for Th17 cells in rheumatoid arthritis. We hypothesized that CD4+CD161+ cells representing Th17 lineage cells may be modulated prior to or after development of clinical synovitis. Therefore, in a cross-sectional study, we investigated the occurrence of CD4+CD161+ T-cells in seropositive arthralgia patients who are at risk for developing rheumatoid arthritis and in newly diagnosed rheumatoid arthritis patients. In a prospective study, we evaluated the effect of methotrexate treatment on circulating CD4+CD161+ T-cells. Next, we assessed if these cells can be detected at the level of the RA joints. Precursor Th17 lineage cells bearing CD161 were found to be increased in seropositive arthralgia patients. In contrast, circulating CD4+CD161+T-cells were decreased in newly diagnosed rheumatoid arthritis patients. The decrease in CD4+CD161+ T-cells correlated inversely with C-reactive protein and with the 66 swollen joint count. Methotrexate treatment led to normalization of CD4+CD161+ T-cells and reduced disease activity. CD4+CD161+ T cells were readily detected in synovial tissues from both early and late-stage rheumatoid arthritis. In addition, synovial fluid from late-stage disease was found to be enriched for CD4+CD161+ T-cells. Notably, synovial fluid accumulated CD4+CD161+T-cells showed skewing towards the Th1 phenotype as evidenced by increased interferon-γ expression. The changes in peripheral numbers of CD4+CD161+ T-cells in seropositive arthralgia and early rheumatoid arthritis and the enrichment of these cells at the level of the joint predict a role for CD4+CD161+ T-cells in the early immune events leading to clinical synovitis. Our findings may add to the development of RA prediction models and provide opportunities for early intervention.

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Related in: MedlinePlus

CD4+CD161+ T-cells are readily detected at the level of the joint in newly diagnosed and in late-stage RA.Detection of T cells expressing CD161 in ST obtained from a newly diagnosed RA patient using IHC on consecutive cryostat sections (Krenn score = 4 [37]). A representative example is shown (magnification 40x). Blanc (A), CD3 (B), CD4 (C), CD161 (D).Analysis of the number of CD4+CD161+ T-cells from paired PB and SF and non-paired PB and ST from late-stage RA. Frequency of CD161+ cells within (E, F) CD4+ and (G, H) CD8+ T-cells were compared between paired samples of PB and SF (n=6; Wilcoxon matched pairs test) or PB and enzyme-digested ST (n=4; Mann-Whitney test).
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pone-0079370-g003: CD4+CD161+ T-cells are readily detected at the level of the joint in newly diagnosed and in late-stage RA.Detection of T cells expressing CD161 in ST obtained from a newly diagnosed RA patient using IHC on consecutive cryostat sections (Krenn score = 4 [37]). A representative example is shown (magnification 40x). Blanc (A), CD3 (B), CD4 (C), CD161 (D).Analysis of the number of CD4+CD161+ T-cells from paired PB and SF and non-paired PB and ST from late-stage RA. Frequency of CD161+ cells within (E, F) CD4+ and (G, H) CD8+ T-cells were compared between paired samples of PB and SF (n=6; Wilcoxon matched pairs test) or PB and enzyme-digested ST (n=4; Mann-Whitney test).

Mentions: CD161 may function as an adhesion molecule and thereby facilitate migration [14,23]. To assess if the observed decrease of circulating CD4+CD161+ T-cells in newly diagnosed RA patients may be explained by their homing to the site of inflammation, we analyzed CD161 expression in ST samples obtained via arthroscopy in this group. CD4+ CD161+ T-cells were readily detected in ST sections using IHC. Representative staining of consecutive synovial biopsy sections showed clear staining for CD161 in the area’s infiltrated by CD3- and CD4- expressing cells (Figure 3A-D).


Circulating CD4+CD161+ T lymphocytes are increased in seropositive arthralgia patients but decreased in patients with newly diagnosed rheumatoid arthritis.

Chalan P, Kroesen BJ, van der Geest KS, Huitema MG, Abdulahad WH, Bijzet J, Brouwer E, Boots AM - PLoS ONE (2013)

CD4+CD161+ T-cells are readily detected at the level of the joint in newly diagnosed and in late-stage RA.Detection of T cells expressing CD161 in ST obtained from a newly diagnosed RA patient using IHC on consecutive cryostat sections (Krenn score = 4 [37]). A representative example is shown (magnification 40x). Blanc (A), CD3 (B), CD4 (C), CD161 (D).Analysis of the number of CD4+CD161+ T-cells from paired PB and SF and non-paired PB and ST from late-stage RA. Frequency of CD161+ cells within (E, F) CD4+ and (G, H) CD8+ T-cells were compared between paired samples of PB and SF (n=6; Wilcoxon matched pairs test) or PB and enzyme-digested ST (n=4; Mann-Whitney test).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3815125&req=5

pone-0079370-g003: CD4+CD161+ T-cells are readily detected at the level of the joint in newly diagnosed and in late-stage RA.Detection of T cells expressing CD161 in ST obtained from a newly diagnosed RA patient using IHC on consecutive cryostat sections (Krenn score = 4 [37]). A representative example is shown (magnification 40x). Blanc (A), CD3 (B), CD4 (C), CD161 (D).Analysis of the number of CD4+CD161+ T-cells from paired PB and SF and non-paired PB and ST from late-stage RA. Frequency of CD161+ cells within (E, F) CD4+ and (G, H) CD8+ T-cells were compared between paired samples of PB and SF (n=6; Wilcoxon matched pairs test) or PB and enzyme-digested ST (n=4; Mann-Whitney test).
Mentions: CD161 may function as an adhesion molecule and thereby facilitate migration [14,23]. To assess if the observed decrease of circulating CD4+CD161+ T-cells in newly diagnosed RA patients may be explained by their homing to the site of inflammation, we analyzed CD161 expression in ST samples obtained via arthroscopy in this group. CD4+ CD161+ T-cells were readily detected in ST sections using IHC. Representative staining of consecutive synovial biopsy sections showed clear staining for CD161 in the area’s infiltrated by CD3- and CD4- expressing cells (Figure 3A-D).

Bottom Line: Precursor Th17 lineage cells bearing CD161 were found to be increased in seropositive arthralgia patients.The decrease in CD4+CD161+ T-cells correlated inversely with C-reactive protein and with the 66 swollen joint count.In addition, synovial fluid from late-stage disease was found to be enriched for CD4+CD161+ T-cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, Groningen, The Netherlands ; Groningen research initiative on healthy ageing and immune longevity (GRAIL), Groningen, The Netherlands.

ABSTRACT
Improved understanding of the immune events discriminating between seropositive arthralgia and clinical synovitis is of key importance in rheumatology research. Ample evidence suggests a role for Th17 cells in rheumatoid arthritis. We hypothesized that CD4+CD161+ cells representing Th17 lineage cells may be modulated prior to or after development of clinical synovitis. Therefore, in a cross-sectional study, we investigated the occurrence of CD4+CD161+ T-cells in seropositive arthralgia patients who are at risk for developing rheumatoid arthritis and in newly diagnosed rheumatoid arthritis patients. In a prospective study, we evaluated the effect of methotrexate treatment on circulating CD4+CD161+ T-cells. Next, we assessed if these cells can be detected at the level of the RA joints. Precursor Th17 lineage cells bearing CD161 were found to be increased in seropositive arthralgia patients. In contrast, circulating CD4+CD161+T-cells were decreased in newly diagnosed rheumatoid arthritis patients. The decrease in CD4+CD161+ T-cells correlated inversely with C-reactive protein and with the 66 swollen joint count. Methotrexate treatment led to normalization of CD4+CD161+ T-cells and reduced disease activity. CD4+CD161+ T cells were readily detected in synovial tissues from both early and late-stage rheumatoid arthritis. In addition, synovial fluid from late-stage disease was found to be enriched for CD4+CD161+ T-cells. Notably, synovial fluid accumulated CD4+CD161+T-cells showed skewing towards the Th1 phenotype as evidenced by increased interferon-γ expression. The changes in peripheral numbers of CD4+CD161+ T-cells in seropositive arthralgia and early rheumatoid arthritis and the enrichment of these cells at the level of the joint predict a role for CD4+CD161+ T-cells in the early immune events leading to clinical synovitis. Our findings may add to the development of RA prediction models and provide opportunities for early intervention.

Show MeSH
Related in: MedlinePlus