RT Journal Article
SR Electronic
T1 Expansion of CD4<sup>+</sup>CD25<sup>+</sup>and FOXP3<sup>+</sup> Regulatory T Cells during the Follicular Phase of the Menstrual Cycle: Implications for Human Reproduction
JF The Journal of Immunology
JO J. Immunol.
FD American Association of Immunologists
SP 2572
OP 2578
DO 10.4049/jimmunol.178.4.2572
VO 178
IS 4
A1 Arruvito, Lourdes
A1 Sanz, Marianela
A1 Banham, Alison H.
A1 Fainboim, Leonardo
YR 2007
UL http://www.jimmunol.org/content/178/4/2572.abstract
AB Regulatory T cells (Tregs) are thought to affect the severity of various infectious and autoimmune diseases. The incidence of autoimmune disease is higher in fertile women than in men. Thus, we investigated whether Treg numbers were modulated during the menstrual cycle by sex hormones. In fertile nonpregnant women, we detected an expansion of CD4+CD25+FOXP3+ Tregs in the late follicular phase of the menstrual cycle. This increase was tightly correlated with serum levels of estradiol and was followed by a dramatic decrease in Treg numbers at the luteal phase. Women who have had recurrent spontaneous abortions (RSA) showed similarly low numbers of Tregs at both the follicular and luteal phases, comparable to numbers we observed in postmenopausal women. In addition to decreased numbers, Tregs from women with RSA were also functionally deficient, as higher numbers were required to exert a similar magnitude of suppression to CD4+CD25+FOXP3+ cells from fertile women. Consequently, reproductive failure might result from the inability of Tregs in women with RSA to expand during the preimplantatory phase combined with their lower functional capacity. Additionally, the modulation of Treg numbers we observed in fertile women suggests that the stage of the menstrual cycle should be taken into account when Treg numbers are investigated clinically.