4.8 Article

Dynamic changes to tissue-resident immunity after MHC-matched and MHC-mismatched solid organ transplantation

Journal

CELL REPORTS
Volume 35, Issue 7, Pages -

Publisher

CELL PRESS
DOI: 10.1016/j.celrep.2021.109141

Keywords

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Funding

  1. University of Western Australia (UWA)
  2. Western Australian State government
  3. Australian Commonwealth government
  4. UWA Animal Care Services
  5. Western Australian Department of Health
  6. Charlies Foundation for Research
  7. Sir Charles Gairdner Hospital
  8. Osborne Park Health Care Group [RAC 2018-19/030]
  9. Australian Government Research Training Program Scholarship
  10. National Health and Medical Research Council Senior Research Fellowship [1139607]
  11. National Health and Medical Research Council of Australia [1139607] Funding Source: NHMRC

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The study shows that after liver and heart transplantation, donor lymphocytes are retained in the liver grafts and peripheral lymphoid organs of the recipients. In MHC-matched transplants, this retention occurs, while in MHC-mismatched transplants, recipient cells infiltrate the graft and deplete donor lymphocytes.
The heterogeneous pool of tissue-resident lymphocytes in solid organs mediates infection responses and supports tissue integrity and repair. Their vital functions in normal physiology suggest an important role in solid organ transplantation; however, their detailed examination in this context has not been performed. Here, we report the fate of multiple lymphocyte subsets, including T, B, and innate lymphoid cells, after murine liver and heart transplantation. In major histocompatibility complex (MHC)-matched transplantation, donor lymphocytes are retained in liver grafts and peripheral lymphoid organs of heart and liver transplant recipients. In MHC-mismatched transplantation, increased infiltration of the graft by recipient cells and depletion of donor lymphocytes occur, which can be prevented by removal of recipient T and B cells. Recipient lymphocytes fail to recreate the native organs' phenotypically diverse tissue-resident lymphocyte composition, even in MHC-matched models. These post-transplant changes may leave grafts vulnerable to infection and impair long-term graft function.

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