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

The retention of donor tissue-resident leucocytes following transplantation is dependent on the level of major and minor histocompatibility (#201)

Sarah Dart 1 , Amy Prosser 1 , Wen Hua Huang 1 , Liu Liu 1 , Jaskirat Kaur 1 , Xiao Zhang 1 , Andrew Lucas 1 , Bastiaan de Boer 2 , Gary Jeffrey 1 , Michaela Lucas 1 3
  1. The University of Western Australia, Nedlands, WA, Australia
  2. Department of Anatomical Pathology, Fiona Stanley Hospital, PathWest, Perth, WA, Australia
  3. Department of Immunology, Sir Charles Gairdner Hospital, PathWest, Perth, WA, Australia

During solid organ transplantation, donor leucocytes, including tissue-resident leucocytes (TRL) are transferred along with the organ itself, which has implications for the post-transplant immune response. However, the factors contributing to TRL retention or depletion after transplantation have not been explored. Given that human liver transplants are not routinely matched for either major histocompatibility complex (MHC) or minor histocompatibility antigen (mH-Ag), we investigated the effect of variations in MHC and mH-Ag mismatch on donor TRL retention and the post-transplant immune response.

We performed orthotopic liver transplants between mice with varying levels of MHC and mH-Ag mismatch, in the absence of immunosuppression. Donor and recipient mice were completely MHC-matched, 50% MHC-matched (haploidentical), completely MHC-mismatched, or completely MHC-matched, with a mH-Ag mismatch. Leucocytes were isolated from the graft and peripheral lymphoid tissues before and after transplantation. Donor and recipient leucocytes were quantified and phenotyped by flow cytometry, distinguishable by differential expression of CD45.1 and CD45.2.

Irrespective of mismatch, donor leucocyte numbers in the graft decreased within one day after transplantation and were detectable in recipient tissues. Simultaneously, recipient leucocytes infiltrated the graft and developed a TRL phenotype. In the MHC-matched model, donor leucocytes were retained until day 7, with those remaining in the graft enriched for a TRL phenotype. This also occurred in mH-Ag mismatched transplants, except that no donor regulatory T cells were detectable in the graft or periphery at day 7. In contrast, in both the complete MHC-mismatch and haploidentical models, no donor leucocytes were detectable after day 4 post-transplantation.

Variations in MHC and mH-Ag mismatch between donors and recipients affect the retention of donor leucocytes after transplantation. The loss of donor leucocytes is likely to have implications for graft infection control, function, and longevity. Thus, further investigations into the mechanisms responsible for their depletion are necessary.