Engelmann Flora, Barron Alex, Urbanski Henryk, Neuringer Martha, Kohama Steven G, Park Byung, Messaoudi Ilhem
Vaccine and Gene Therapy Institute, Oregon Health and Science University, 505 NW 185th Avenue, Beaverton, OR 09006, USA.
Age (Dordr). 2011 Sep;33(3):275-89. doi: 10.1007/s11357-010-9178-0. Epub 2010 Sep 3.
Aging is associated with a general dysregulation in immune function, commonly referred to as "immune senescence". Several studies have shown that female sex steroids can modulate the immune response. However, the impact of menopause-associated loss of estrogen and progestins on immune senescence remains poorly understood. To help answer this question, we examined the effect of ovariectomy on T-cell homeostasis and function in adult and aged female rhesus macaques. Our data show that in adult female rhesus macaques, ovariectomy increased the frequency of naïve CD4 T cells. In contrast, ovariectomized (ovx) aged female rhesus macaques had increased frequency of terminally differentiated CD4 effector memory T cells and inflammatory cytokine-secreting memory T cells. Moreover, ovariectomy reduced the immune response (T-cell cytokine and IgG production) following vaccination with modified vaccinia ankara in both adult and aged female rhesus macaques compared to ovary-intact age-matched controls. Interestingly, hormone therapy (estradiol alone or in conjunction with progesterone) partially improved the T-cell response to vaccination in aged ovariectomized female rhesus macaques. These data suggest that the loss of ovarian steroids, notably estradiol and progesterone, may contribute to reduced immune function in post-menopausal women and that hormone therapy may improve immune response to vaccination in this growing segment of the population.
衰老与免疫功能的普遍失调有关，通常被称为“免疫衰老”。多项研究表明，女性性激素可调节免疫反应。然而，绝经相关的雌激素和孕激素丧失对免疫衰老的影响仍知之甚少。为了回答这个问题，我们研究了卵巢切除术对成年和老年雌性恒河猴T细胞稳态和功能的影响。我们的数据显示，成年雌性恒河猴卵巢切除术后，初始CD4 T细胞频率增加。相反，卵巢切除的老年雌性恒河猴终末分化的CD4效应记忆T细胞和分泌炎性细胞因子的记忆T细胞频率增加。此外，与年龄匹配的未切除卵巢的对照组相比，成年和老年雌性恒河猴接种改良安卡拉痘苗后，卵巢切除术降低了免疫反应（T细胞细胞因子和IgG产生）。有趣的是，激素疗法（单独使用雌二醇或与孕酮联合使用）部分改善了老年卵巢切除雌性恒河猴对疫苗接种的T细胞反应。这些数据表明，卵巢类固醇尤其是雌二醇和孕酮的丧失可能导致绝经后女性免疫功能下降，并且激素疗法可能改善这一不断增长的人群对疫苗接种的免疫反应。
