Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark.
Blood. 2011 Feb 10;117(6):1861-8. doi: 10.1182/blood-2010-07-298992. Epub 2010 Dec 16.
Pregnancy represents a major challenge to immunologic tolerance. How the fetal "semiallograft" evades maternal immune attack is unknown. Pregnancy success may involve alteration of both central (thymic) and peripheral tolerance mechanisms. HIV infection is characterized by CD4(+) T-cell depletion, chronic immune activation, and altered lymphocyte subsets. We studied immunologic consequences of pregnancy in 20 HIV-infected women receiving highly active antiretroviral therapy (HAART), and for comparison in 16 HIV-negative women. Lymphocyte subsets, thymic output, and cytokine profiles were measured prospectively during pregnancy and postpartum. A significant expansion of CD4(+)CD25(+)CD127(low)FoxP3(+) regulatory T cells indicating alteration of peripheral tolerance was seen during second trimester, but only in HIV-negative women. HIV-infected women had lower CD4 counts, lower thymic output and Th-2 cytokines, and more immune activation at all time points compared with controls. Immune activation was decreased in HIV-infected patients during pregnancy. In contrast, CD4 counts were increased in both groups. In conclusion, the study does not indicate that pregnancy adversely affects the immunologic course of HIV infection. However, despite HAART during pregnancy, HIV-infected women display different immunologic profiles from HIV-negative women, which may have importance for the induction of fetal-maternal tolerance and in part explain the increased risk of abortion in HIV-infected women.
妊娠对免疫耐受是一个重大挑战。胎儿的“半同种异体移植物”如何逃避母体免疫攻击尚不清楚。妊娠的成功可能涉及到中枢（胸腺）和外周耐受机制的改变。HIV 感染的特征是 CD4(+)T 细胞耗竭、慢性免疫激活和淋巴细胞亚群改变。我们研究了 20 名接受高效抗逆转录病毒治疗（HAART）的 HIV 感染妇女妊娠期间及产后的免疫后果，并与 16 名 HIV 阴性妇女进行了比较。前瞻性地测量了妊娠和产后期间的淋巴细胞亚群、胸腺输出和细胞因子谱。在 HIV 阴性妇女中，在妊娠中期观察到 CD4(+)CD25(+)CD127(low)FoxP3(+)调节性 T 细胞的显著扩增，表明外周耐受发生改变。与对照组相比，HIV 感染妇女在所有时间点的 CD4 计数较低、胸腺输出和 Th2 细胞因子较低、免疫激活程度较高。与对照组相比，HIV 感染患者的免疫激活在妊娠期间降低。相反，两组的 CD4 计数均增加。总之，该研究并未表明妊娠对 HIV 感染的免疫过程产生不利影响。然而，尽管在妊娠期间接受了 HAART，HIV 感染妇女的免疫谱与 HIV 阴性妇女不同，这可能对诱导胎儿-母体耐受具有重要意义，并在一定程度上解释了 HIV 感染妇女流产风险增加的原因。
