Transplantation of Tissue-Resident Lymphocytes
Amy Prosser1,2, Wen Hua Huang3, Liu Liu1, Bastiaan de Boer4, Irma Larma-Cornwall5, Gary Jeffrey1, Silvana Gaudieri2, Axel Kallies6, Michaela Lucas1,7.
1School of Medicine, University of Western Australia, Perth, Australia; 2School of Anatomy, Physiology and Human Biology, University of Western Australia, Perth, Australia; 3School of Surgery, University of Western Australia, Perth, Australia; 4Department of Anatomical Pathology, PathWest, Perth, Australia; 5Centre for Microscopy, Characterisation and Analysis, University of Western Australia, Perth, Australia; 6Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia; 7School of Pathology and Laboratory Medicine, University of Western Australia, Perth, Australia
The importance of donor lymphocytes to the induction of tolerance to solid organ allografts was identified in the 1990s, however specific cell subsets and their individual roles have not been investigated. Recently described tissue-resident (TR) lymphocytes, including tissue-resident memory T (Trm), innate lymphoid cells (ILC), γδ T, invariant natural killer T (iNKT) and mucosal-associated invariant T (MAIT) cells are likely to be transferred with the graft and impact the outcome of transplantation.
We have developed an orthotopic liver transplant model in mice to track donor-derived tissue-resident cells and assess the impact of these cells on transplant outcome. Analysis of liver lymphocytes is conducted using three 15-16 colour flow cytometry panels. Using the same techniques, we are also able to examine the recipient immune response and the differentiation of alloreactive lymphocytes to a tissue-resident phenotype.
Donor-derived tissue-resident lymphocytes are maintained within the transplanted liver of congenically matched donor and recipient mice. MHC mismatched transplants, however, resulted in variable survival of donor lymphocyte subsets. Differentiation of vast numbers of graft-infiltrating recipient-derived lymphocytes to a tissue-resident phenotype was also observed.
Differential depletion of specific donor lymphocyte subsets in a mismatch context and the establishment of tissue-residency by recipient lymphocytes may provide some insight into the mechanisms of rejection of solid organs.
