Prenatal allogeneic tolerance in mice remains stable despite potent viral immune activation

Beverly S I Strong, Katherine O. Ryken, Amanda E. Lee, Lucas E. Turner, Ram K. Wadhwani, Tess J. Newkold, Amir M. Alhajjat, Jonathan W. Heusel, Aimen F. Shaaban*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Transplanting stem cells before birth offers an unparalleled opportunity to initiate corrective treatment for numerous childhood diseases with minimal or no host conditioning. Although long-term engraftment has been demonstrated following in utero hematopoietic cellular transplantation during immune quiescence, it is unclear if prenatal tolerance becomes unstable with immune activation such as during a viral syndrome. Using a murine model of in utero hematopoietic cellular transplantation, the impact of an infection with lymphocytic choriomeningitis virus on prenatal allospecific tolerance was examined. The findings in this report illustrate that established mechanisms of donor-specific tolerance are strained during potent immune activation. Specifically, a transient reversal in the anergy of alloreactive lymphocytes is seen in parallel with the global immune response toward the virus. However, these changes return to baseline following resolution of the infection. Importantly, prenatal engraftment remains stable during and after immune activation. Collectively, these findings illustrate the robust nature of allospecific tolerance in prenatal mixed chimerism compared with models of postnatal chimerism and provides additional support for the prenatal approach to the treatment of congenital benign cellular disease.

Original languageEnglish (US)
Pages (from-to)4001-4009
Number of pages9
JournalJournal of Immunology
Issue number8
StatePublished - Oct 15 2015

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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