Enomoto Laura M, Kloberdanz Keelie J, Mack Doug G, Elizabeth Deepa, Weinberg Adriana
University of Colorado Health Sciences Center, Denver, CO 80262, USA.
J Acquir Immune Defic Syndr. 2007 Jun 1;45(2):137-43. doi: 10.1097/QAI.0b013e3180471bae.
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.
为确定激素避孕疗法（HCT）期间达到的雌激素和孕酮浓度对HIV感染和未感染受试者细胞介导免疫（CMI）的影响，对水痘-带状疱疹病毒（VZV）血清阳性个体的外周血单个核细胞（PBMC）用0.1 ng/mL雌二醇、33 ng/mL炔诺孕酮和13 ng/mL地塞米松进行处理，并检测VZV CMI。雌激素和孕酮降低了VZV淋巴细胞增殖及辅助性T细胞（Th）1/炎性细胞因子分泌，尽管作用小于地塞米松。孕酮降低了CD8和CD14细胞上CD69激活标志物的表达，并增加了CD14单核细胞上Fas配体（CD178）的表达，提示凋亡诱导可能有助于该激素的抑制作用。分离的CD4、CD8和CD14细胞的细胞因子产生证实了孕酮对所有3种细胞类型均有作用，而雌激素的作用仅限于CD14单核细胞。与未感染受试者（雌激素和孕酮分别降低12%和19%）相比，HIV感染受试者中雌激素和孕酮介导的Th1/炎性细胞因子抑制作用更强（两种激素均降低35%），而对增殖和PBMC表型的作用在HIV状态方面无差异。总体而言，HCT浓度的雌激素和孕酮下调了HIV感染和未感染受试者的体外VZV CMI。
