Ex vivo effect of estrogen and progesterone compared with dexamethasone on cell-mediated immunity of HIV-infected and uninfected subjects
Ex vivo effect of estrogen and progesterone compared with dexamethasone on cell-mediated immunity of HIV-infected and uninfected subjects
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DOI：
10.1097/qai.0b013e3180471bae
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发表时间：
2007-06-01
影响因子：
3.6
通讯作者：
Weinberg, Adriana
中科院分区：
文献类型：
--
作者：
Enomoto, Laura M.;Kloberdanz, Keelie J.;Weinberg, Adriana
为了确定激素避孕治疗（HCT）期间达到的雌激素和孕激素浓度对HIV感染和未感染受试者的细胞介导免疫（CMI）的影响，用0.1 ng/mL雌二醇、33 ng/mL炔诺孕酮和13 ng/mL地塞米松处理水痘带状疱疹病毒（VZV）血清阳性个体的外周血单核细胞（PBMC），并检测VZV CMI。雌激素和孕激素降低VZV淋巴细胞增殖和辅助性T细胞（Th）1/炎性细胞因子分泌，但低于地塞米松。孕酮降低CD 8（+）和CD 14（+）细胞表面CD 69活化标志物的表达，增加CD 14（+）单核细胞表面Fas配体（CD 178）的表达，提示孕酮的抑制作用可能与诱导细胞凋亡有关。分离的CD 4（+）、CD 8（+）和CD 14（+）细胞的细胞因子产生证实了孕酮对所有3种细胞类型的影响，而雌激素的影响仅限于CD 14（+）单核细胞。与未感染受试者（雌激素和孕酮分别为12%和19%）相比，HIV感染受试者中雌激素和孕酮介导的Th 1/炎性细胞因子抑制作用更大（两种激素均降低35%），而对增殖和PBMC表型的影响并不因HIV状态而异。总的来说，雌激素和孕激素的HCT浓度下调了HIV感染和未感染受试者的离体VZV CMI。
To define the effect of estrogen and progesterone concentrations achieved during hormonal contraceptive therapy (HCT) on cell-mediated immunity (CMI) of HIV-infected and uninfected subjects, peripheral blood mononuclear cells (PBMCs) from varicella-zoster virus (VZV)-seropositive individuals were treated with 0.1 ng/mL of estradiol, 33 ng/mL of norgestrel, and 13 ng/mL of dexamethasone and tested for VZV CMI. Estrogen and progesterone decreased VZV lymphocyte proliferation and T helper (Th) 1/inflammatory cytokine secretion, albeit less than dexamethasone. Progesterone decreased the expression of CD69 activation marker on CD8(+) and CD14(+) cells and increased the expression of Fas ligand (CD178) on CD14(+) monocytes, suggesting that induction of apoptosis may contribute to the inhibitory effect of this hormone. Cytokine production of separated CD4(+), CD8(+), and CD14(+) cells confirmed the effect of progesterone on all 3 cellular types, whereas the effect of estrogen was restricted to CD14(+) monocytes. The estrogen- and progesterone-mediated inhibition of Th1/inflammatory cytokines was greater in HIV-infected subjects (35% decrease for both hormones) compared with uninfected subjects (12% and 19% for estrogen and progesterone, respectively), whereas the effect on proliferation and PBMC phenotype did not differ by HIV status. Overall, HCT concentrations of estrogen and progesterone downregulated ex vivo VZV CMI of HIV-infected and uninfected subjects.