Liver tissue-resident lymphocytes are significantly heterogeneous, and the original repertoire is not recreated by infiltrating recipient cells
Amy Prosser1,2, Wen Hua Huang3, Sarah Dart1, Monalyssa Watson1, Liu Liu1, Bastiaan de Boer4, Axel Kallies5, Michaela Lucas1.
1Medical School, University of Western Australia, Perth, Australia; 2School of Human Sciences, University of Western Australia, Perth, Australia; 3School of Surgery, University of Western Australia, Perth, Australia; 4Department of Anatomical Pathology, PathWest, Perth, Australia; 5Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, Melbourne, Australia
Introduction: Tissue-resident (TR) lymphocytes play an unknown but likely significant role in the outcome of solid organ transplantation due to their localisation and low activation threshold. Phenotypic identification of TR cells is limited by organ-specific protein expression and the perhaps incorrect presumption of subset homogeneity. The definition and destiny of these lymphocytes after transplantation has not previously been shown. The liver is the ideal organ in which to study TR lymphocytes due to the abundance of all currently known populations.
Methods: Orthotopic liver transplants were performed between MHC matched or mismatched donor and recipient mice. No immunosuppressant drugs were administered to any animal. Graft rejection was assessed by an experienced histopathologist. Donor- and recipient-derived lymphocytes were detected and analysed from grafted livers, bone marrow (BM), spleen, lymph nodes (LN) and blood by flow cytometry.
Results: Each lymphocyte subset analysed contained a proportion of TR cells that were retained long-term after MHC matched transplantation. Surprisingly, TR T cells were largely heterogeneous in phenotype, variability which has not previously been appreciated. After MHC mismatched transplantation all donor-derived TR lymphocytes were deleted. Analysis of recipient-derived graft-infiltrating lymphocytes revealed nil to limited proportions of these cells gained a TR phenotype, instead continuing to circulate through the graft.
Conclusion: We have described in detail the retention and phenotypic profile of TR lymphocytes after liver transplantation. Despite loss of some to all TR lymphocytes, infiltrating recipient-derived lymphocytes do not recreate the original TR population repertoire. The ability of the graft to fight infection may therefore be hindered by the lack of these first line defenders.
Charlies Foundation for Research. Sir Charles Gairdner Osborne Park Health Care Group Research Advisory Committee.
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