Annals of the Rheumatic Diseases 2008;67:984-990
EXTENDED REPORTS
Pregnancy induces numerical and functional changes of CD4+CD25high regulatory T cells in patients with rheumatoid arthritis
Department of Rheumatology and Clinical Immunology and Allergology, Inselspital, University of Bern, Bern, Switzerland
F Förger, Department of Nephrology, Klinikum rechts der Isar, Technische Universität München, Ismaninger St. 22, 81675 Munich, Germany; Frauke.Foerger{at}lrz.tu-muenchen.de
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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