Follow-up examination of 12 heart transplant recipients with cardiac CT

Xiamen Board of Health's Medical Research Program, China [SK 0622]Objective: The aims of this study were to observe the changes of a transplanted heart with cardiac computed tomography (CT) and to evaluate the clinical application of the examination. Methods: Cardiac CT was performed on 12 heart transplant recipients, of which 4 cases were also examined by echocardiography. Coronary arteries, the cardiac chamber, and the wall were shown with three-dimensional imaging techniques, and their changes were analyzed and discussed. Results: Twelve heart transplant recipients were successfully examined by CT. All transplanted hearts were found with good anastomosis at the great vessels and atria. Coronary allograft vasculopathy was found in 7 cases, of which 4 cases were found with ventricular dilation or ventricular septum thickening and 1 with tricuspid regurgitation. Ventricular dilation was found in other 3 cases, of which 1 was found with ventricular septum thickening and 1 with tricuspid regurgitation. No abnormality was found by cardiac CT in the rest 2 cases, which were found with mitral regurgitation by echocardiography. Conclusion: Cardiac CT can clearly and directly display the changes in the shape of a transplanted heart and coronary artery abnormalities. It will become an ideal noninvasive follow-up method for the heart transplant recipients. (c) 2012 Elsevier Inc. All rights reserved

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

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 oil 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 ill 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

Rapamycin or tacrolimus alone fails to resist cardiac allograft accelerated rejection mediated by alloreactive CD4(+) memory T cells in mice

Key Project of Program of Science and Technology of Fujian Province of China [MKJ 2008-59]Donor-reactive memory T (Tm) cells undermine transplanted organs more readily than naive T cells. Rapamycin (RAPA) and tacrolimus (FK-506) are current mainstay immunosuppressants used for preventing acute allograft rejection. Although their efficacy in suppressing naive T cell is established, their suppressing effect on memory T cells is undefined. This study was conducted to investigate the inhibiting capability of RAPA or FK-506 against transferred alloreactive CD4(+) Tm, cells in a mouse cardiac transplant model. We found that these drugs alone prolonged the median survival time (MST) of allograft from 5 days to 9 days in recipient mice with CD4(+) Tm infusion (P < 0.01), which however was not significantly longer than that (8 days) in untreated recipient mice without CD4(+) Tm infusion (naive control). Mean histologic rank of rejection activity in section of cardiac allograft on day 5 postgrafting was Grade 4 in the Tm control recipients versus Grade 3A in both of the immunosuppressant treatment recipients with CD4(+) Tm infusion. RAPA or FK-506 alone failed to completely suppress proliferation and differentiation of the alloreactive CD4(+) Tm, which was confirmed by in vitro mixed lymphocyte reaction (MLR) and by flow cytometry (FCM) of the splenocytes for detecting CD44(high)CD62L(-) effector/memory as well as CD69(+)/CD25(+) activation phenotype cells from the respective recipients. Furthermore, the agent alone didn't completely inhibit the activation of CD4(+) Tm, for serum level of IFN-gamma and its gene expression at the cardiac allograft from the immunosuppressant-treated recipients were as still high as the untreated naive control. Thus, RAPA or FK-506 alone couldn't completely suppress the proliferation and activation of the alloantigen-primed CD4(+) Tm cells responding to the alloantigen, indicating that alloreactive CD4(+) Tm was insensitive to these immunosuppressants. The characteristics of alloreactive CD4(+) Tm to resist immunosuppressants and its potency to initiate quick and vigorous rejection despite treatment with the immunosuppressant make it to be a critical barrier to prolongation of allograft survival and induction of transplant tolerance. (C) 2009 Elsevier B.V. All rights reserved