Effect of CD4+ Memory T Cells on Rejection Response of Ectopic Heart Transplantation in Mice

Zhao, Yongxiang; Zhang, Shan; Li, Qiang; Zhou, Yuan; Zeng, Xiaocong; Qing, Fan; Liao, Chenxi; Lü, Xiaoling; Liu, J.

doi:10.1016/j.transproceed.2010.12.054

Cited by 5 publications

(3 citation statements)

References 16 publications

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“…This is in accordance with previous findings that B cells and their products play a central role in graft injury (30). These results are in accordance with Zhao et al (47) who revealed that especially CD4 + T mem cells, that mediate acute rejection, are insensitive to short-term CsA in heart transplantation in mice. We observed that only permanent low-dose CsA prevented acute and chronic allograft rejection.…”

Section: Discussionsupporting

confidence: 93%

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Permanent CNI Treatment for Prevention of Renal Allograft Rejection in Sensitized Hosts Can Be Replaced by Regulatory T Cells

Siepert

Ahrlich

Vogt

et al. 2012

American Journal of Transplantation

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Recent data suggest that donor-specific memory T cells (T mem ) are an independent risk factor for rejection and poor graft function in patients and a major challenge for immunosuppression minimizing strategies. Many tolerance induction protocols successfully proven in small animal models e.g. costimulatory blockade, T cell depletion failed in patients. Consequently, there is a need for more predictive transplant models to evaluate novel promising strategies, such as adoptive transfer of regulatory T cells (Treg).We established a clinically more relevant, lifesupporting rat kidney transplant model using a high responder (DA to LEW) recipients that received donorspecific CD4 + / 8 + GFP + T mem before transplantation to achieve similar pre-transplant frequencies of donorspecific T mem as seen in many patients. T cell depletion alone induced long-term graft survival in naïve recipients but could not prevent acute rejection in T mem + rats, like in patients. Only if T cell depletion was combined with permanent CNI-treatment, the intragraft inflammation, and acute/chronic allograft rejection could be controlled long-term. Remarkably, combining 10 days CNI treatment and adoptive transfer of Tregs (day 3) but not Treg alone also induced longterm graft survival and an intragraft tolerance profile (e.g. high TOAG-1) in T mem + rats. Our model allows evaluation of novel therapies under clinically relevant conditions.

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Section: Discussionsupporting

confidence: 93%

“…Several studies demonstrate that control of memory is a major challenge in transplantation (24)(25)(26)(27)(28)(29)(30)(31)(32)(33). CNI remain the cornerstones to control T mem .…”

Section: Introductionmentioning

confidence: 99%

Permanent CNI Treatment for Prevention of Renal Allograft Rejection in Sensitized Hosts Can Be Replaced by Regulatory T Cells

Siepert

Ahrlich

Vogt

et al. 2012

American Journal of Transplantation

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“…It has also been reported that infusion of sensitized memory CD4+ T cells produces acute rejection in mice that have undergone abdominal heterotopic heart transplantation. In addition, infusion of sensitized memory CD4+ T cells has been shown to significantly shorten the survival times of transplanted hearts, and this effect cannot be reversed by commonly used immunosuppressants ( 12 , 13 ). Clinical studies have shown that the prognoses of patients who have undergone liver transplantation are dependent on patient CD8+ T memory cell status ( 14 ).…”

Section: Introductionmentioning

confidence: 99%

CD147 blockade as a potential and novel treatment of graft rejection

Luan

Zhao

Zhang

et al. 2017

Molecular Medicine Reports

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Cluster of differentiation (CD)147 is highly involved in the T cell activation process. High CD147 expression is observed on the surfaces of activated T cells, particularly CD4+ T cells. In organ transplantation, it is important to prevent graft rejection resulting from the excessive activation of T cells, particularly CD4+ T cells, which exhibit a key role in amplifying the immune response. The present study aimed to investigate the effects of CD147 blockade in vitro and in vivo and used a transplant rejection system to assess the feasibility of utilizing CD147 antibody-based immunosuppressant drugs for the treatment of graft rejection. The effects of CD147 antibodies were evaluated on lymphocyte proliferation stimulated by phytohemagglutinin or CD3/CD28 magnetic beads and in a one-way mixed lymphocyte reaction (MLR) system in vitro. For the in vivo analysis, an allogeneic skin transplantation mouse model was used. CD147 antibodies were effective against lymphocytes, particularly CD4+T lymphocytes, and were additionally effective in the one-way MLR system. In the allogeneic skin transplantation mouse model, the survival of transplanted skin was extended in the CD147 antibody-treated group. Furthermore, the level of inflammatory cell infiltration in transplanted skin was reduced. CD147 blockade decreased the serum levels of interleukin (IL)-17 and the proportions of peripheral blood CD4+ and CD8+ memory T cells. The data demonstrated that CD147 blockade suppressed skin graft rejection, primarily by suppressing CD4+T and memory T cell proliferation, indicating that CD147 exhibits great potential as a target of immunosuppressant drugs.

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Preoperative application of combination of portal venous injection of donor spleen cells and intraperitoneal injection of rapamycin prolongs the survival of cardiac allografts in mice

Gong

Sha

et al. 2017

Asian Pacific Journal of Tropical Medicine

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Effect of CD4+ Memory T Cells on Rejection Response of Ectopic Heart Transplantation in Mice

Cited by 5 publications

References 16 publications

Permanent CNI Treatment for Prevention of Renal Allograft Rejection in Sensitized Hosts Can Be Replaced by Regulatory T Cells

Permanent CNI Treatment for Prevention of Renal Allograft Rejection in Sensitized Hosts Can Be Replaced by Regulatory T Cells

CD147 blockade as a potential and novel treatment of graft rejection

Preoperative application of combination of portal venous injection of donor spleen cells and intraperitoneal injection of rapamycin prolongs the survival of cardiac allografts in mice

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