Pregnancy induces numerical and functional changes of CD4+CD25high regulatory T cells in patients with rheumatoid arthritis

Förger, F., Marcoli, N., Gadola, S., Möller, B., Villiger, P.M. and Østensen, M. (2007) Pregnancy induces numerical and functional changes of CD4+CD25high regulatory T cells in patients with rheumatoid arthritis. Annals of the Rheumatic Diseases, 67 (7), 984-990. (doi:10.1136/ard.2007.075283).

Abstract

OBJECTIVE: In a prospective study we investigated whether numerical and functional changes of CD4+CD25(high) 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+CD25(high) T cells was determined by flow cytometry in 12 patients with RA and 14 healthy women during and after pregnancy. FACS-sorted CD4+CD25(high) 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+CD25(high) Treg were significantly higher in the third trimester compared to 8 weeks post-partum both in patients and controls. Numbers of CD4+CD25(high) Treg inversely correlated with disease activity in the third trimester and post-partum. In co-culture experiments significantly higher amounts of IL-10 and lowered levels of TNFalpha and IFNgamma were found in supernatants of the third trimester compared to post-partum samples. These findings were independent from health or disease in pregnancy, however post-partum TNFalpha and IFNgamma 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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