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ORIGINAL ARTICLE: Syngeneic Immune‐Dependent Abortions in Mice Suggest Paternal Alloantigen‐Independent Mechanisms
Author(s) -
Kundert Jean A.,
Sealey Amy L.,
Li Yan,
Capecchi Mario R.,
Schmidt Edward E.
Publication year - 2008
Publication title -
american journal of reproductive immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.071
H-Index - 97
eISSN - 1600-0897
pISSN - 1046-7408
DOI - 10.1111/j.1600-0897.2008.00622.x
Subject(s) - haplotype , biology , immune system , major histocompatibility complex , allele , immunology , abortion , histocompatibility , antigen , immune tolerance , zygote , fetus , gene , genetics , andrology , pregnancy , human leukocyte antigen , medicine , embryogenesis
Problem Recurrent 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 study Sib‐crosses of C57Bl/6J (haplotype b/b) mice heterozygous for a targeted hypomorphic allele of the tbp gene ( tbp ΔΝ/+ ) resulted in selective mid‐gestational abortion of 88% of the tbp ΔΝ/ΔΝ fetuses. In dams lacking mature lymphocytes ( rag1 −/− ), nearly all tbp ΔΝ/ΔΝ fetuses survived to birth, indicating abortions were immune‐dependent. Allogeneic pregnancies bearing tbp ΔΝ/ΔΝ fetuses were established by either hybridizing the paternal lineage to BALB/cJ (haplotype d/d) and mating hybrid tbp ΔΝ/+ sires to haplotype b/b tbp ΔΝ/+ C57Bl/6J dams, or by transfer of haplotype b/b zygotes from tbp ΔΝ/+ × tbp ΔΝ/+ matings into pseudopregnant wild‐type CByD2F1/J dams (haplotype d/d). Results Neither hemizygous paternal allogeneic loci nor homozygous allogeneic loci, including a haplotype‐mismatched major histocompatibility complex (MHC), increased abortion frequencies. Conclusion Results 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.