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Effects of progestin-only contraceptives on the phenotype and function of female reproductive tract CD4+ and CD8+ T cells


Use of progestin-only contraceptives may enhance the susceptibility of the female reproductive tract (FRT) to HIV infection. We assessed the effects of progestin-only contraceptives, including Depo-Provera (DMPA), and the levonorgestrel intra-uterine system (LNG iUS) on endometrial and endocervical mucosa of premenopausal women.


Participants using either DMPA (n=15) or the LNG iUS (n=19) for at least 3 months and women using no hormonal contraceptives (n=24) were recruited. Endocervical curettage, endocervical cytobrush, and endometrial biopsy were obtained from all women. Expression of T cell activation markers, memory/effector differentiation markers and HIV co receptors were assessed by multiparameter flow cytometry. CD4+ and CD8+ T cells producing CD107a, IL-10, IL-2, IFNγ, MIP1β and IL-17 were measured after stimulation with PMA/ionomycin or staphylococcal enterotoxin B (SEB).


Endometrial CD4+ and CD8+ T cells and endocervical CD8+ T cells were highly activated in women using LNG iUS as compared to controls. Compared to DMPA, LNG iUS resulted in increased activation of endocervical curettage CD4+ T cells. CXCR4+CCR5+CD4+ T cells in the endometrium and curettage were increased in women using LNG iUS as compared to controls. The percentage of endocervical central memory CD4+ and CD8+ T cells were decreased in LNG iUS recipients. Following SEB stimulation, endometrial CD4+ T cells responded with production of IL-10, IL-2 and IL-17. CD8+ T cells produced elevated percentages of IL-10 in women using LNG iUS compared to control women.


LNG iUS and DMPA affected endocervical and endometrial T cell phenotype and responsiveness to polyclonal stimulation. Further studies are warranted to clarify the effects of contraceptive products on upper FRT immune cells and HIV susceptibility.

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Correspondence to Uma Shanmugasundaram.

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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

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Shanmugasundaram, U., Critchfield, J., Pannell, J. et al. Effects of progestin-only contraceptives on the phenotype and function of female reproductive tract CD4+ and CD8+ T cells. BMC Infect Dis 14 (Suppl 3), O21 (2014).

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  • Levonorgestrel
  • DMPA
  • Hormonal Contraceptive
  • Endometrial Biopsy
  • Female Reproductive Tract