Liver transplantationOutcomeγδT Cells Are Involved in Liver Transplant Tolerance
Section snippets
Materials and Methods
Male C57BL/10 (B10; H2b) and C3H/HeJ (C3H; H2k) mice purchased from Jackson Laboratory (Bar Harbor, Maine, United States) were housed in a specific pathogen-free facility under a protocol approved by the Institutional Animal Care and Use Committee. Orthotopic liver transplantation (OLT) was performed from B10 to C3H mice as previously described.8, 9 Cohorts of animals received either anti-CTLA4 mAb (UC10-4F10-11; Chimerigen, Allston, Mass, United States; 250 μg/mouse, days 0, 2, 4, IP) or
Results
Liver grafts from B10 donors were spontaneously accepted by C3H recipients without immunosuppression. Compared with control IgG-treated recipients (mean survival time [MST] >100 days), liver grafts were acutely rejected by recipients that received anti-CD25 mAb either pre- (MST 14.9 ± 9.8 days; n = 8; P < .01) or posttransplantation (MST 16.8 ± 12.6 days; n = 6; P < .01) or anti-CTLA4 mAb (MST 8.5 ± 3.6 days; n = 6), or combined treatment (MST 7.8 ± 1.6 days; n = 5; P < .01). In naïve C3H mice,
Discussion
While the contribution of circulating and tissue-specific γδT cells is firmly established in a wide variety of innate mechanisms,1, 2, 3 their roles in adaptive and autoimmune responses continue to emerge.3, 10 The contribution of γδT cells to solid organ transplantation immunology has not been studied extensively: the presence of γδT cells in the blood of transplant patients has been associated with stable liver or kidney allograft function.5, 6 A preponderance of Vδ1 γδT cells was associated
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Cited by (14)
Characteristics of Vδ1<sup>+</sup> and Vδ2<sup>+</sup> γδ T cell subsets in acute liver allograft rejection
2013, Transplant ImmunologyCitation Excerpt :Vδ1+ γδ T cells, predominant in tissue such as that in the spleen, intestine, and liver, possess regulatory and effector properties; Vδ2+ γδ T cells, which are the main subset of γδ T cells in the peripheral blood, possess defense properties against pathogens [15]. An animal study showed that the total percentage of γδ T cells decreased in a spontaneously tolerated liver graft, and increased in a liver allograft rejected after anti-CTLA4 or anti-CD25 monoclonal antibody administration [14]. In humans, γδ T cells have been reported to be involved in renal allograft rejection; γδ T cells also participate in cardiac allograft acceptance [16,17].
Regulatory functions of γδ T cells
2013, International ImmunopharmacologyCitation Excerpt :In this context, liver transplantation is of special interest as operational tolerance (i.e. a status where immunosuppressive therapy can be weaned) is observed in 15 to 20% of liver allograft recipients. In a mouse model of allogeneic liver transplantation, Malone and co-workers observed a significantly reduced proportion of intrahepatic γδ T cells in spontaneously tolerated liver grafts, whereas intrahepatic γδ T cell numbers increased when organ rejection was induced [56]. While these studies suggest that γδ T cells might contribute to allograft rejection, other observations point to a regulatory function of γδ T cells in organ transplantation.
Potential role of γδ T cell-derived IL-17 in acute cardiac allograft rejection
2012, Annals of Thoracic SurgeryTranscriptomic Analysis Identifies A Tolerogenic Dendritic Cell Signature
2021, Frontiers in ImmunologyDeciphering the Contribution of γδ T Cells to Outcomes in Transplantation
2018, Transplantation
This work was supported by funding from the Division of Transplantation, Department of Surgery, and the Provost Bridge Fund of the University of Washington, Seattle, Washington, USA.