Syngeneic immune-dependent abortions in mice suggest paternal alloantigen-independent mechanisms.

Abstract

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(deltaN/+)) resulted in selective mid-gestational abortion of 88% of the tbp(deltaN/deltaN) fetuses. In dams lacking mature lymphocytes (rag1-/-), nearly all tbp(deltaN/deltaN) fetuses survived to birth, indicating abortions were immune-dependent. Allogeneic pregnancies bearing tbp(deltaN/deltaN) fetuses were established by either hybridizing the paternal lineage to BALB/cJ (haplotype d/d) and mating hybrid tbp(deltaN/+) sires to haplotype b/b tbp(deltaN/+) C57Bl/6J dams, or by transfer of haplotype b/b zygotes from tbp(deltaN/+)x tbp(deltaN/+) 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.

• Authors: Jean A Kundert, Amy L Sealey, Yan Li, Mario R Capecchi, Edward E Schmidt
• Journal: American journal of reproductive immunology (New York, N.Y. : 1989) (Am J Reprod Immunol) Vol. 60 Issue 4 Pg. 290-7 (Oct 2008) ISSN: 1046-7408 [Print] Denmark
• PMID: 18759828 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Isoantigens

Topics

• Abortion, Threatened (genetics, immunology)
• Animals
• Female
• Immune Tolerance
• Isoantigens (genetics, immunology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Knockout
• Pregnancy