γδ T Cell Receptor Deficiency Attenuated Cardiac Allograft Vasculopathy and Promoted Regulatory T cell Expansion

Abstract

Abstractcd T cell comprises about 5% of the overall T cell population, and they differ from conventional ab T cells. Previous studies have indicated the contribution of cd T cell to acute allograft rejection, but the role of cd T cell in cardiac allograft vasculopathy (CAV) is not investigated. Hearts of adult B6.C-H-2 bm12 KhEg were heterotopically transplanted into major histocompatibility complex (MHC) class II-mismatched C57BL/6 mice (wild-type, cd TCR À/À ), which is an established murine model of chronic allograft rejection without immunosuppression. The survival of grafts was monitored daily by abdominal palpation until the complete cessation of cardiac contractility. Our current study demonstrated that cd T cell receptor (TCR) deficiency significantly attenuated CAV, and this effect coincides with low expression of Hmgb1, IFN-c and IL-17 while increased number of CD4 + CD25 + Foxp3 + regulatory T cells, and depletion of regulatory T cells abrogated the prolonged allograft survival induced by cd TCR deficiency. cd TCR deficiency resulted in attenuated CAV and prolonged graft survival in murine models of cardiac transplantation, and this effect was associated with enhanced expansion of regulatory T cells.

HMGB1 Is Involved in Chronic Rejection of Cardiac Allograft via Promoting Inflammatory-Like mDCs

“…In single MHC-II mismatched models (in brief, MHC-II mismatched models), bm12 mice were used as donors and B6 mice were used as recipients. This is an established murine model of chronic allograft rejection without immunosuppressive treatment (22). After surgery, allograft impulse was assessed by daily abdominal palpation.…”

Vγ4 γδ T Cells Provide an Early Source of IL-17A and Accelerate Skin Graft Rejection

“…IL-17A is an essential mediator of inflammatory responses and is known to promote cardiac allograft rejection (Kimura et al, 2012). It has been previously reported that gd T cells are the predominant early source of IL-17A in allograft rejection (Kimura et al, 2012;Wang et al, 2012;Zhu et al, 2013). Despite the association of gd T cells with graft rejection, the exact role of gd T-cell-derived IL-17A remains unknown.…”

“…IL-17A is essential for Vg4 T-cell-mediated skin graft rejection Activated gd T cells rapidly produce large amounts of IFN-g and IL-17A, which play critical roles in allograft rejection (Chen et al, 2007;Wang et al, 2012;Zhu et al, 2013). To determine the role of IL-17A and IFN-g in skin graft rejection, we examined skin graft survivals in WT recipients treated with IFN-g or IL-17A neutralizing antibodies three times on days 0, 2, and 4 after transplantation.…”

An Immune Atlas of T Cells in Transplant Rejection: Pathways and Therapeutic Opportunities

“…148 Unsurprisingly, given the abundance of evidence for a key role of IL-17 in allograft rejection, infiltration of IL-17producing γδ T cells has been associated with promotion of allograft rejection, 149,150 and depletion associated with attenuation of rejection. 151 In addition to prolonged allograft survival, depletion of γδ T cells has also been associated with enhanced accumulation of immunoregulatory Foxp3 + Treg. 151 In humans, γδ T cells are broadly classified as Vδ2 positive or negative, based on the TCR δ chain.…”

“…151 In addition to prolonged allograft survival, depletion of γδ T cells has also been associated with enhanced accumulation of immunoregulatory Foxp3 + Treg. 151 In humans, γδ T cells are broadly classified as Vδ2 positive or negative, based on the TCR δ chain. The Vδ2 cells are the predominate circulating subset, comprising >70% of γδ T cells in peripheral circulation.…”