The Recall Alloresponse Following Retransplantation is More Intense Compared with the T cell Memory-Transfer Model

Abstract

The presence of alloreactive memory T cells in recipient is a critical handicap to achieving transplantation tolerance. To make a mouse model that can as closely as possible mimic the presensitized transplant patient is important for research on this subject. Thus, we developed a novel retransplant model and compared the alloresponse in this model with that in the memory T cells-transfer model (transfer control). Mean survival time of allograft was compared between 3 groups, including blank transplant control, memory transfer control and retransplant groups. Cellular rejection activity in allografts was evaluated via HE staining of cardiac graft section. Proliferation and differentiation of the alloreactive effector T cells were assayed by in vitro mixed lymphocyte reaction and flow cytometry, respectively. Real-time quantitive RT-PCR was used to assess gene expression of cytokines and surum IFN-gamma was measured via ELISA. It showed that the median survival time of allograft in retransplant recipients was significantly shortened compared to that of transfer control, and it was the same in rejection score of graft. Moreover, proliferation and differentiation of the alloreactive effector T cells were more intensive in retransplant recipients than that in transfer control, which was confirmed by in vitro mixed lymphocyte reaction and by flow cytometry of the splenocytes for detecting CD44highCD62L- memory/effector phenotype cells. Furthermore, activation of CD4+ memory T cells is reflected by high level of surum IFN-gamma and the intensive gene expression of IFN-gamma and IL-2 at cardiac allograft in retransplant recipients. Collectively, the recall alloresponse in retransplantation is more intensive than that in a memory-transfer setting, and this retransplant model is closer to the clinic situation than the memory-transfer model in rodents.

Inhibition of C‑X‑C motif chemokine 10 reduces graft loss mediated by memory CD8+ T cells in a rat cardiac re‑transplant model

“…In parallel with the increase in CXCL10, the proportion of CD8 + Tm cells in splenocytes was also elevated. These results provided evidence that accelerated rejection mediated by CD8 + Tm cells is a crucial factor in re-transplantation (23)(24)(25) -, refers to Tm cells that display effector functions so that they provide rapid protection after antigen reencounter (29,30) as well as trafficking between spleen and non-lymphoid tissue. By definition, this increased propensity to activation, coupled with a shortened lag time to enter the cell cycle and acquire effector functions, allows Tm cells to quickly and robustly exert an effective recall response (31).…”

CXCL9 and CXCL10 accelerate acute transplant rejection mediated by alloreactive memory T cells in a mouse retransplantation model

“…However, the role of CXCL9 and CXCL10 in retransplantation models remains unknown. The model used in the present study is known to closely mimic the clinical setting, as a quicker and more vigorous alloresponse is induced compared with other models (20). In the present study, this retransplantation model was used to determine whether the levels of CXCL9 and/or CXCL10 increase post-transplantation.…”

Indoleamine 2,3-Dioxygenase and Metabolites Protect Murine Lung Allografts and Impair the Calcium Mobilization of T Cells

“…Compared with Tn, Tem responded more rapidly to lower concentrations of antigen, and were less dependent upon costimulation. Not only are memory cells more resistant to apoptosis, with a relatively long lifespan, but they are also more resistant to suppression by alloreactive regulatory T cells and resistant to immunosuppressive agents (30,31). Therefore, therapies that reduce the generation of Tem may be beneficial in maintaining lung allograft survival.…”