Bizargity Peyman, Bonney Elizabeth A
Department of Obstetrics, Gynecology and Reproductive Sciences, University of Vermont College of Medicine, Burlington, VT, USA.
Immunology. 2009 Apr;126(4):565-78. doi: 10.1111/j.1365-2567.2008.02918.x. Epub 2008 Sep 5.
Recent advances in our understanding of dendritic cells (DCs) and their role in tolerance and immunity has fuelled study of their normal development and function within the reproductive tract. The common hypothesis that pregnancy is a state of immune suppression or deviation now includes the idea that alterations in DC phenotype and function are critical for maternal tolerance. We chose to study DCs in the uterus and lymphoid tissue in non-pregnant and pregnant mice at mid-gestation to understand what DC-related factors may be involved in premature birth. We used a mouse model where the mother's immune system has been shown to respond to the male antigen H-Y. Observed differences among DCs in the uterus, uterine draining nodes and spleen, even in non-pregnant mice, suggest the existence of a specialized uterus-specific subset of DCs. We further found that, amongst CD45(+) CD11c(+) cells in the uterus and peripheral lymphoid tissue of pregnant mice, expression of major histocompatibility complex class II (MHC II) and costimulatory molecules (i.e. CD80) was similar to that in the non-pregnant state. Moreover, there was no pregnancy-related decrease in the proportion of CD11c(+) cells in the uterus or in the uterine node that were CD11b(-) CD8(+). Pregnancy increased the CD11b(+) subsets and the expression of chemokine (C-C motif) ligand 6 (CCL6) in DCs of the uterine draining nodes. Finally, DC subsets showed variable expression, with respect to tissue and pregnancy, of the cytokine interleukin-15, which is important in lymphoid cell homeostasis. For DCs, pregnancy is not a state of immune paralysis, but of dynamic developmental change.
我们对树突状细胞(DCs)及其在耐受性和免疫中作用的理解取得了最新进展,这推动了对其在生殖道内正常发育和功能的研究。关于妊娠是一种免疫抑制或免疫偏离状态的普遍假设,现在包含了DC表型和功能的改变对母体耐受性至关重要这一观点。我们选择研究妊娠中期未孕和孕鼠子宫及淋巴组织中的DCs,以了解哪些与DC相关的因素可能与早产有关。我们使用了一种小鼠模型,其中已证明母亲的免疫系统会对雄性抗原H-Y作出反应。即使在未孕小鼠中,观察到子宫、子宫引流淋巴结和脾脏中的DCs存在差异,这表明存在一种专门的子宫特异性DC亚群。我们进一步发现,在孕鼠子宫和外周淋巴组织中的CD45(+) CD11c(+)细胞中,主要组织相容性复合体II类(MHC II)和共刺激分子(即CD80)的表达与未孕状态相似。此外,子宫或子宫淋巴结中CD11c(+)细胞中CD11b(-) CD8(+)的比例没有与妊娠相关的下降。妊娠增加了子宫引流淋巴结中DCs的CD11b(+)亚群和趋化因子(C-C基序)配体6(CCL6)的表达。最后,DC亚群在细胞因子白细胞介素-15的表达上,因组织和妊娠状态而异,白细胞介素-15在淋巴细胞稳态中很重要。对于DCs来说,妊娠不是一种免疫麻痹状态,而是一种动态的发育变化状态。