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;
- Accepted 2 October 2007
- Published Online First 30 October 2007
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)α and interferon (IFN)γ were found in supernatants of the third trimester compared to postpartum samples. These findings were independent from health or disease in pregnancy, however postpartum TNFα and IFNγ 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.
Competing interests: None.
Funding: Supported by a grant from the Technische Universität of München HWP grant number SSZ-3/203/04, the Olga Maienfisch Fund and the Swiss National Funds, grant number 320000-111936.
Ethics approval: Informed consent was sought and the study was approved by the ethics committee of the University of Bern.