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

Amy Prosser; Wen Hua Huang; Liu Liu; Sarah Dart; Monalyssa Watson; Bastiaan de Boer; Philip Kendrew; Andrew Lucas; Irma Larma-Cornwall; Silvana Gaudieri; Gary P Jeffrey; Luc Delriviere; Axel Kallies; Michaela Lucas

doi:10.1016/j.celrep.2021.109141

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

Cell Rep. 2021 May 18;35(7):109141. doi: 10.1016/j.celrep.2021.109141.

Authors

Affiliations

¹ Medical School, University of Western Australia, Perth, WA 6009, Australia; School of Human Sciences, University of Western Australia, Perth, WA 6009, Australia.
² Medical School, University of Western Australia, Perth, WA 6009, Australia; Western Australian Liver and Kidney Transplant Service, Sir Charles Gairdner Hospital, Perth, WA 6009, Australia.
³ Medical School, University of Western Australia, Perth, WA 6009, Australia.
⁴ Department of Anatomical Pathology, Pathwest Laboratory Medicine, Perth, WA 6009, Australia.
⁵ Department of Clinical Biochemistry, Pathwest Laboratory Medicine, Perth, WA 6009, Australia.
⁶ Centre for Microscopy, Characterisation and Analysis, University of Western Australia, Perth, WA 6009, Australia.
⁷ School of Human Sciences, University of Western Australia, Perth, WA 6009, Australia.
⁸ Medical School, University of Western Australia, Perth, WA 6009, Australia; Western Australian Liver and Kidney Transplant Service, Sir Charles Gairdner Hospital, Perth, WA 6009, Australia; Department of Gastroenterology, Sir Charles Gairdner Hospital, Perth, WA 6009, Australia.
⁹ Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
¹⁰ Medical School, University of Western Australia, Perth, WA 6009, Australia; Department of Immunology, Sir Charles Gairdner Hospital and Pathwest Laboratory Medicine, Perth, WA 6009, Australia. Electronic address: michaela.lucas@uwa.edu.au.

PMID: 34010637
DOI: 10.1016/j.celrep.2021.109141

Abstract

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.

Keywords: heart transplantation; innate lymphoid cell; liver transplantation; tissue-resident lymphocyte; unconventional T cell.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Humans
Immunity, Innate / immunology*
Major Histocompatibility Complex / genetics*
Mice
Organ Transplantation / methods*