Syngeneic immune-dependent abortions in mice suggest paternal alloantigen-independent mechanisms.
Syngeneic immune-dependent abortions in mice suggest paternal alloantigen-independent mechanisms.
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小鼠同基因免疫依赖性流产表明不依赖父本同种异体抗原的机制。
DOI：
10.1111/j.1600-0897.2008.00622.x
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发表时间：
2008
期刊：
影响因子：
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通讯作者：
Schmidt,EdwardE
中科院分区：
文献类型：
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作者：
Kundert,JeanA;Sealey,AmyL;Li,Yan;Capecchi,MarioR;Schmidt,EdwardE
问题人类反复免疫相关性流产被认为是由母体对父亲同种异体抗原的免疫反应引起的。我们研究了父系同种异体抗原在免疫依赖性流产小鼠模型中的作用。研究方法：将tbp基因的一个靶向亚型等位基因（tbpΔ N/+）杂合的C57 Bl/6 J（单倍型B/B）小鼠进行S1 B-杂交，导致88%的tbp Δ N/Δ N胎儿选择性妊娠中期流产。在缺乏成熟淋巴细胞（rag 1 −/−）的母鼠中，几乎所有tbp Δ N/Δ N胎儿存活至出生，表明流产是免疫依赖性的。通过将父系血统与BALB/cJ杂交，建立携带tbp Δ N/Δ N胎儿的异基因妊娠。（单倍型d/d）并将杂交bp Δ N/+父系与单倍型B/btbpΔ N/+ C57 Bl/6 J母鼠交配，或通过将单倍型B/B合子从tbp Δ N/+×tbpΔ N/+交配转移到假孕野生型CByD 2 F1/J母鼠中结果无论是半合子父系同种异体基因座还是纯合子同种异体基因座，包括单倍型错配的主要组织相容性复合体（MHC），结论结果表明，母体对父本同种异体抗原（包括错配的MHC抗原）的耐受机制在这些妊娠中是完整的，但发生了母体免疫依赖性父本抗原非依赖性突变体流产。这些数据表明，在某些免疫介导的流产病例中，父方同种异体抗原的存在可能是偶然的，并且对于损害排斥反应是多余的。
ProblemRecurrent immune‐associated miscarriages in humans are thought to result from maternal immune responses to paternal alloantigens. We investigated the role of paternal alloantigens in a mouse model of immune‐dependent abortion.Method of studySib‐crosses of C57Bl/6J (haplotype b/b) mice heterozygous for a targeted hypomorphic allele of thetbpgene (tbpΔΝ/+) resulted in selective mid‐gestational abortion of 88% of thetbpΔΝ/ΔΝfetuses. In dams lacking mature lymphocytes (rag1−/−), nearly alltbpΔΝ/ΔΝfetuses survived to birth, indicating abortions were immune‐dependent. Allogeneic pregnancies bearingtbpΔΝ/ΔΝfetuses were established by either hybridizing the paternal lineage to BALB/cJ (haplotype d/d) and mating hybridtbpΔΝ/+sires to haplotype b/btbpΔΝ/+C57Bl/6J dams, or by transfer of haplotype b/b zygotes fromtbpΔΝ/+×tbpΔΝ/+matings into pseudopregnant wild‐type CByD2F1/J dams (haplotype d/d).ResultsNeither hemizygous paternal allogeneic loci nor homozygous allogeneic loci, including a haplotype‐mismatched major histocompatibility complex (MHC), increased abortion frequencies.ConclusionResults suggested that mechanisms for maternal tolerance of paternal alloantigens, including mismatched MHC antigens, were intact in these pregnancies, yet maternal immune‐dependent paternal antigen‐independent abortion of mutants occurred. These data indicate that, in some cases of immune‐mediated abortions, the presence of paternal alloantigens can be coincidental and superfluous to the compromising rejection response.