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Women taking combined oral contraceptives (COCs), however, show large variabilities in the magnitudes of their antibody responses. The goal of the present study was to determine the effects of 17\u03b2-estradiol (E2) and progesterone (P4) alone and in combination on the cellular immune response to HPV type 16 (HPV-16) VLPs<jats:italic>in vitro<\/jats:italic>. Peripheral blood mononuclear cells (PBMCs) from healthy donor women were stimulated<jats:italic>in vitro<\/jats:italic>with HPV-16 VLPs (2.5 \u03bcg\/ml) in the presence of E2 and P4 administered either alone or in combination; and lymphoproliferation, cytokine production, transcription factor expression, and steroid hormone receptor expression were analyzed. HPV-16 VLPs significantly increased the levels of lymphoproliferation, proinflammatory cytokine (gamma interferon [IFN-\u03b3], interleukin-1\u03b2 [IL-1\u03b2], IL-2, IL-6, IL-8, IL-12p70, IL-17, tumor necrosis factor alpha [TNF-\u03b1]) production, anti-inflammatory cytokine (IL-1ra, IL-10) production, and the expression of Er\u03b1 and Er\u03b2 but decreased the levels of<jats:italic>Foxp3<\/jats:italic>expression and production of transforming growth factor \u03b2 (TGF-\u03b2). Exposure of PBMCs to E2 and P4 either alone or in combination significantly decreased the levels of lymphoproliferation and production of proinflammatory cytokines (IFN-\u03b3, IL-12p70, TNF-\u03b1) but increased the levels of production of IL-10 and TGF-\u03b2 and the expression of<jats:italic>Foxp3<\/jats:italic>in response to HPV-16 VLPs. Treatment of cells with biologically relevant concentrations of sex steroid hormones suppressed the inflammatory response and enhanced the regulatory response to HPV-16 VLPs, which may have implications for predicting the long-term efficacy of HPV vaccines, adverse events, and cross-protection among women taking COCs.<\/jats:p>","DOI":"10.1128\/cvi.00441-09","type":"journal-article","created":{"date-parts":[[2010,2,4]],"date-time":"2010-02-04T02:56:55Z","timestamp":1265252215000},"page":"609-617","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":29,"title":["Progesterone and 17\u03b2-Estradiol Enhance Regulatory Responses to Human Papillomavirus Type 16 Virus-Like Particles in Peripheral Blood Mononuclear Cells from Healthy Women"],"prefix":"10.1128","volume":"17","author":[{"given":"Morgan A.","family":"Marks","sequence":"first","affiliation":[{"name":"Department of Epidemiology"},{"name":"W. 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