Background The long-term fate of maternal T cells primed by fetal antigen during pregnancy has not been well studied but may have significant impact for female transplant recipients. Although it has been predicted that these cells adopt a memory fate, recent data suggest that immunoregulatory mechanisms which dominate during pregnancy may alter fate decisions. We asked whether fetal antigen promoted the differentiation of canonical allospecific memory CD8+ T cells that pose a threat to an allograft. Methods Ova-specific OT-1 CD45.2+ congenic CD8+ T cells were adoptively transferred into Act-mOVA-mated pregnant CD45.1 B6 mice. CD8+ OT-1 T cell phenotype and cytokine production were analyzed 30 days after pup delivery. In additional experiments, congenic OT-1 T cells were sorted from parous mice and adoptively transferred into RAGKO recipients that subsequently received an Ova skin graft. Results Ova fetal antigen primed Ova-specific OT-1 T cells to divide and produce IFNgamma during pregnancy. These CD44+ antigen-experienced cells persisted in the repertoire of parous animals and expressed elevated levels of PD-1. When stimulated ex vivo with Ova peptide, these cells made substantially less IFNgamma than memory control animals that had been sensitized with a prior Ova skin graft (35% vs. 75%; p<.01). However, 100% of T cell deficient RAGKO mice that were transferred OT-1 T cells from parous mice rapidly rejected Ova skin grafts (Mean survival time: 8 days). Conclusion Antigen-experienced, PD-1 expressing CD8+ T cells primed during pregnancy persist in the repertoire of parous animals. Despite limited cytokine producing capacity and an altered phenotype compared to canonical memory T cells, these cells maintain adequate cytotoxicity to pose a threat to an organ transplant.

CITATION INFORMATION: Porrett P, Xu R, Wherry E. Fate and Function of CD8+ T Cells Primed by Fetal Antigen During Pregnancy. Am J Transplant. 2017;17 (suppl 3).

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