Tolerance to Noninherited Maternal MHC Antigens in Mice

Joachim Andrassy, Satoshi Kusaka, Ewa Jankowska-Gan, Jose R. Torrealba, Lynn D. Haynes, Brodie R. Marthaler, Robert C. Tam, Ben M W Illigens, Natalie Anosova, Gilles Benichou, William J. Burlingham

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90 Scopus citations

Abstract

The phenomenon of tolerance to noninherited maternal Ags (NIMA) is poorly understood. To analyze the NIMA effect C57BL/6 (H-2b/b) males were mated with B6D2F1 (H-2b/d) females, whereby 50% of the offspring are H-2b/b mice that have been exposed to maternal H-2 d alloantigens. Controls were H-2b/b offspring of C57BL/6 mothers, either inbred C57BL/6 mice or F1 backcross mice from breedings with H-2b/d fathers. We found that 57% of the H-2 b/b offspring of semiallogeneic (H-2b/d) mothers accepted fully allogeneic DBA/2 (H-2d/d) heart grafts for >180 days, while similar transplants were all rejected by day 11 in controls (p < 0.0004). Foster nursing studies showed that both oral and in utero exposure to NIMA are required for this tolerogenic effect. An effect of NIMA was also found to extend the survival of skin grafts from a semiallogeneic donor (p < 0.02). Pretransplant analysis of splenocytes showed a 40-90% reduction of IL-2-, IL-5-, and IFN-γ-producing T cells responding to H-2d-expressing APC in NIMAd-exposed vs control mice. Injection of pregnant BALB/c-dm2 (H-2Ld-negative) female mice i.v. with H-2Ld 61-80 peptide profoundly suppressed the offspring's indirect pathway alloreactive CD4+ T cell response to H-2Ld. These results suggest that the natural exposure of the fetus and newborn to maternal cells and/or soluble MHC Ags suppresses NIMA-allospecific T cells of the offspring, predisposing to organ transplant tolerance in adult mice.

Original languageEnglish (US)
Pages (from-to)5554-5561
Number of pages8
JournalJournal of Immunology
Volume171
Issue number10
DOIs
StatePublished - Nov 15 2003

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Andrassy, J., Kusaka, S., Jankowska-Gan, E., Torrealba, J. R., Haynes, L. D., Marthaler, B. R., Tam, R. C., Illigens, B. M. W., Anosova, N., Benichou, G., & Burlingham, W. J. (2003). Tolerance to Noninherited Maternal MHC Antigens in Mice. Journal of Immunology, 171(10), 5554-5561. https://doi.org/10.4049/jimmunol.171.10.5554