IMMUNOLOGY2024™ Conference Recordings-Allogeneic conflict in pregnancy and transplantation

Video Transcription

Video Summary

The speaker explored why pregnancy creates immune tolerance to a fetus, while transplantation of the same “foreign” antigens is usually rejected. He described an apparent paradox: pregnancy is tolerogenic, yet it also induces HLA antibodies in many women, which can later increase transplant rejection risk and reduce access to organs.<br /><br />Using mouse models, the lab found that pregnancy can generate fetus-specific IgG antibodies, and that fetal antigen tolerance can extend to a fetus-matched heart transplant only when B cells and antibodies are absent. Transfer of postpartum serum or postpartum B cells restored graft rejection, showing that humoral immunity can override tolerance.<br /><br />The second major theme was how pregnancy affects memory T cells. In preliminary human studies, early pregnancies were associated with weak fetus-specific T-cell responses, but women with many pregnancies sometimes showed sensitized responses. In mice, however, prior sensitization followed by pregnancy led to CD8 memory cells that became hypofunctional/exhausted and supported long-term graft acceptance. This was linked to increased exhaustion markers (TOX, PD1, LAG3, TIGIT), transcriptional changes, and epigenetic remodeling, especially at the Tox locus.<br /><br />Overall, the talk proposed that pregnancy can both induce immune tolerance and reshape memory T cells in ways that may be harnessed to improve transplant tolerance.

Keywords

pregnancy tolerance

transplant rejection

HLA antibodies

fetal antigen

B cells

memory T cells

immune exhaustion