Donor-reactive T cells and innate immune cells promote pig-to-human decedent xenograft rejection 2254507
<title>Abstract</title> Xenotransplantation of pig organs is a promising solution to the organ shortage; however, rejection remains a major obstacle. Pig-to-human decedent transplantation provides an opportunity to study immune barriers to xenotransplantation experimentally. We tracked donor-reactive T cell dynamics in a 61-day pig-to-human decedent thymokidney xenotransplant. Xenogeneic donor-reactive T cell clones (XDRTCCs) identified using high-throughput <italic>TCRB</italic> CDR3 sequencing expanded markedly in peripheral blood in association with apparent antibody-mediated rejection (AMR). Single-cell RNA and TCR sequencing of leukocytes from the xenograft showed XDRTCC infiltration and effector transcript expression during AMR. Additionally, γδ and NK cells with cytotoxic effector phenotypes were prominent in the rejecting xenograft. These data suggest that improved suppression of innate immunity and T cell responses might enhance the success of xenotransplantation.
Authors
- Farshid Fathi (ORCID: https://orcid.org/0000-0002-0280-7612)
- Е. S. Novikova (ORCID: https://orcid.org/0000-0001-6004-9111)
- Jacqueline I. Kim (ORCID: https://orcid.org/0000-0001-8165-525X)
- Yasmeen S. Saad (ORCID: https://orcid.org/0000-0001-6612-7985)
- Ian Jaffe (ORCID: https://orcid.org/0000-0002-7309-308X)
- Robert A. Montgomery (ORCID: https://orcid.org/0000-0001-5894-0589)
- Imad Aljabban (ORCID: https://orcid.org/0000-0003-1231-1159)
- Kevin Breen
- Ramin S. Herati (ORCID: https://orcid.org/0000-0003-2613-4050)
- Christopher A. Parks (ORCID: https://orcid.org/0000-0002-2772-2965)
- Jeffrey Stern (ORCID: https://orcid.org/0000-0001-5588-0357)
- Lars Burdorf (ORCID: https://orcid.org/0000-0001-8943-4750)
- Constanza Bay (ORCID: https://orcid.org/0000-0003-2827-3580)
- Nathan Suek
- Benjamin Vermette (ORCID: https://orcid.org/0000-0003-4292-1281)
- Karen Khalil (ORCID: https://orcid.org/0000-0001-7350-0418)
- M. Sykes
- Elizabeth Severa
Institutions
- Columbia University Irving Medical Center (US)
- NYU Langone Health (US)
- Triangle (US)
- United Therapeutics (United States) (US)
- Miami Transplant Institute (US)
- New York University (US)
- Columbia University (US)
Publication Details
- Journal
- The Journal of Immunology
- Published
- 2026-07-28
- DOI
- https://doi.org/10.1093/jimmun/vkag141.226
- Citations
- 5
- Primary Topic
- Xenotransplantation and immune response
- Type
- article
- Field-Weighted Citation Impact
- 10.50
Funders
- New York University
- United Therapeutics Corporation
- National Institutes of Health
- National Center for Advancing Translational Sciences