Research Centre for Reproductive Health, School of Paediatric and Reproductive Health, University of Adelaide, Adelaide, SA 5005, Australia.
J Reprod Immunol. 2010 Dec;87(1-2):1-13. doi: 10.1016/j.jri.2010.05.007. Epub 2010 Jul 8.
Studies in mice demonstrate that the maternal T cell repertoire is aware of paternal antigens during pregnancy, but in healthy pregnancy reactive T cells do not mediate anti-fetal immunity. Mice expressing transgenic T cell receptors (TCRs) specific for paternal and conceptus antigens are powerful tools for elucidating the events surrounding paternal antigen presentation to the maternal T cell repertoire, the nature of the ensuing T cell response and the factors that skew the response towards immune tolerance to allow survival and development of the conceptus. While results from different transgenic TCR models are not always consistent, there is now sufficient data to allow a consensus interpretation that maternal antigen presenting cells present initially seminal fluid antigens and later placenta-derived antigens to both the CD4+ and CD8+ T cell repertoire. T cell proliferation is generally followed by entry into a state of anergy demonstrated by decreased cytokine production and hyporesponsiveness upon restimulation. Some models also demonstrate downregulation of the TCR and co-stimulatory molecules, clonal deletion of paternal antigen-reactive T cells, or alternatively T cell ignorance of paternal antigens. This review will summarise the range of transgenic TCR studies that have shed light on the events surrounding paternal antigen presentation and the various T cell responses to insemination and pregnancy. The benefits, limitations and caveats of these models, and their impact upon data interpretation, are discussed.
在小鼠研究中表明，母体 T 细胞库在怀孕期间就已经对父系抗原有所认知，但在健康妊娠中，反应性 T 细胞不会介导针对胎儿的免疫。表达针对父系和胚胎抗原的转基因 T 细胞受体（TCRs）的小鼠是阐明父系抗原呈递给母体 T 细胞库的周围事件、随之而来的 T 细胞反应的性质以及使反应向免疫耐受倾斜以允许胚胎存活和发育的因素的有力工具。虽然来自不同转基因 TCR 模型的结果并不总是一致，但现在已经有足够的数据可以进行共识解释，即母体抗原呈递细胞最初呈递精液抗原，然后呈递胎盘衍生抗原给 CD4+和 CD8+T 细胞库。T 细胞增殖通常伴随着进入无能状态，表现为细胞因子产生减少和再刺激时反应性降低。一些模型还表明 TCR 和共刺激分子的下调、对父系抗原反应性 T 细胞的克隆删除，或者 T 细胞对父系抗原的无知。这篇综述将总结一系列转基因 TCR 研究，这些研究阐明了父系抗原呈递的周围事件以及对授精和妊娠的各种 T 细胞反应。讨论了这些模型的优势、局限性和注意事项，以及它们对数据解释的影响。
