New Investigator Symposium Presentation 49th Annual Scientific Meeting of the Australian and New Zealand Society for Immunology 2021

Tissue-resident immunity is altered after liver transplantation (#64)

Amy Prosser 1 , Wen Hua Huang 1 , Liu Liu 1 , Sarah Dart 1 , Monalyssa Watson 1 , Bastiaan de Boer 2 , Andrew Lucas 1 , Silvana Gaudieri 1 , Gary Jeffrey 1 3 4 , Luc Delriviere 3 , Axel Kallies 5 , Michaela Lucas 1 6
  1. University of Western Australia, Nedlands, WA, Australia
  2. Department of Anatomical Pathology, PathWest Laboratory Medicine, Perth, WA, Australia
  3. Western Australian Liver and Kidney Transplant Service, Sir Charles Gairdner Hospital, Perth, WA, Australia
  4. Department of Gastroenterology, Sir Charles Gairdner Hospital, Perth, WA, Australia
  5. Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
  6. Department of Immunology, Sir Charles Gairdner Hospital, Perth, WA, Australia

Tissue-resident lymphocytes are present in all solid organs tested thus far and play important physiological roles in mediating infection responses and tissue repair. Whist it is known that donor lymphocytes can persist in immunosuppressed human recipients of solid organ transplantation, the fate and function of tissue-resident lymphocytes in transplantation has not been investigated in detail. Tissue-resident lymphocytes are abundant in the liver, with their parenchymal localisation, memory phenotype and functional potential marking them as prime candidates for influencing transplantation outcome. We have performed liver transplantation in congenic, MHC-matched and -mismatched mice and in-depth phenotyping of donor- and recipient-derived lymphocytes. We have tracked the fate of tissue-resident donor lymphocytes and the response of recipient lymphocytes for up to one month after transplantation. Normal, untransplanted livers contained a myriad of tissue-resident lymphocytes with distinct, often non-canonical phenotypes. In MHC-matched transplants, donor lymphocytes were retained in the graft long term, most notably unconventional T cells such as natural killer T cells. All donor lymphocytes were completely deleted within 7 days of MHC-mismatched transplantation, though this deletion was preventable by removal of recipient T and B cells. Infiltration of significant numbers of recipient lymphocytes occurred to both MHC-matched and, to a greater extent, -mismatched liver grafts. However, these recipient lymphocytes were unable to recreate the normal liver lymphocyte composition, phenotype, and function, even in MHC-matched transplants. The changes that occur to tissue-resident immunity in an organ after transplantation may leave them vulnerable to infection, impair graft function, and impact on graft longevity.