Expansion of CD4+CD25+and FOXP3+ regulatory T cells during the follicular phase of the menstrual cycle: implications in human reproduction

ARRUVITO L, SANZ M, BANHAM A.H Y FAINBOIM

JOURNAL OF IMMUNOLOGY

AMER ASSOC IMMUNOLOGISTS

Año: 2007 vol. 178 p. 2572 - 2578

0022-1767

<!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman";} @page Section1 {size:595.3pt 841.9pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:35.4pt; mso-footer-margin:35.4pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> Regulatory T cells (Tregs) are thought to affect the severity of various infectious and autoimmune diseases and their higher incidence in women. Thus, we addressed the question concerning whether Treg numbers could be modulated during the menstrual cycle by sexual hormones. In fertile non-pregnant women we detected an expansion of CD4+CD25+FOXP3+ Tregs at the late follicular phase of the menstrual cycle. This increase was tightly correlated with serum levels of estrogens and was followed by a dramatic fall in Treg numbers at the luteal phase. Women suffering from recurrent spontaneous abortions (RSA) showed similar numbers of Tregs at both the follicular and luteal phase, comparable to numbers we observed in post-menopausal women. In addition to decreased numbers, Tregs from RSA patients were also functionally deficient, because higher numbers were required to exert a similar magnitude of suppression to CD4+CD25+FOXP3+ cells from fertile women. The inability of Tregs from RSA patients to expand during the pre-implantatory phase, plus their lower functional capacity might contribute to reproductive failure. Additionally, the modulation of Treg numbers we observed in fertile women suggests their stage of the menstrual cycle should be taken into account when Treg numbers are investigated within a clinical setting.