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RESEARCH - Pregnancy induces numerical and functional changes of CD4+CD25high regulatory T cells in patients with RA

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Published Online First: 30 October 2007. doi:10.1136/ard.2007.075283

ls of the Rheumatic Diseases 2008;67:984-990

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EXTENDED REPORTS

Pregnancy induces numerical and functional changes of CD4+CD25high

regulatory T cells in patients with rheumatoid arthritis

F Förger , N Marcoli , S Gadola , B Möller , P M Villiger , M Østensen

Department of Rheumatology and Clinical Immunology and Allergology,

Inselspital, University of Bern, Bern, Switzerland

Objective: In a prospective study we investigated whether numerical

and functional changes of CD4+CD25high regulatory T cells (Treg) were

associated with changes of disease activity observed during pregnancy

and post partum in patients with rheumatoid arthritis (RA).

Methods: The frequency of CD4+CD25high T cells was determined by flow

cytometry in 12 patients with RA and 14 healthy women during and after

pregnancy. Fluorescence-activated cell sorting (FACS) was used to sort

CD4+CD25high T cells and CD4+CD25– T cells were stimulated with

anti-CD3 and anti-CD28 monoclonal antibodies alone or in co-culture to

investigate proliferation and cytokine secretion.

Results: Frequencies of CD4+CD25high Treg were significantly higher in

the third trimester compared to 8 weeks post partum in patients and

controls. Numbers of CD4+CD25high Treg inversely correlated with

disease activity in the third trimester and post partum. In co-culture

experiments significantly higher amounts of IL10 and lowered levels of

tumour necrosis factor (TNF) and interferon (IFN) were found in

supernatants of the third trimester compared to postpartum samples.

These findings were independent from health or disease in pregnancy,

however postpartum TNF and IFN levels were higher in patients with

disease flares.

Conclusion: The amelioration of disease activity in the third

trimester corresponded to the increased number of Treg that induced a

pronounced anti-inflammatory cytokine milieu. The pregnancy related

quantitative and qualitative changes of Treg suggest a beneficial

effect of Treg on disease activity.

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http://ard.bmj.com/cgi/content/abstract/67/7/984?etoc

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