Combination of monoclonal antibodies with DST inhibits accelerated rejection mediated by memory T cells to induce long-lived heart allograft acceptance in mice

Shao, Wei; Chen, Jibing; Dai, Helong; Peng, Yuanzheng; Wang, Feng; Xia, Junjie; Thorlacius, Henrik; Zhu, Qi; Qi, Zhongquan

doi:10.1016/j.imlet.2011.03.009

Cited by 5 publications

(7 citation statements)

References 31 publications

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“…In allogeneic islet and heart transplant models, the combination of DST with multiple mAb exhibited synergistic inhibition effects on the expansion of Tm cells and induced Tm cells to be anergy, thereby prolonged the graft survival time. 34,35 As reported in previous report, 36 DST plus anti-CD45RB mAb can induce Tregs production. Moreover, antigeninduced Tregs can suppress allograft rejection mediated by memory CD8 + T cells.…”

Section: Discussionsupporting

confidence: 54%

“…The DST or whole blood transfusion combined with co‐stimulatory pathway blockades can prolong graft survival in rodent organ transplantations. Wei et al 34 combined DST with anti‐CD40L/LFA‐1/anti‐CD44 agents, they found that the combination can synergistically inhibit accelerated rejection mediated by Tm cells and induce long‐lived heart allograft acceptance in mice. In allogeneic islet and heart transplant models, the combination of DST with multiple mAb exhibited synergistic inhibition effects on the expansion of Tm cells and induced Tm cells to be anergy, thereby prolonged the graft survival time 34 , 35 .…”

Section: Discussionmentioning

confidence: 99%

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Anti‐CD45RB and donor‐specific spleen cells transfusion inhibition allograft skin rejection mediated by memory T cells

Jian

et al. 2016

Immunol Cell Biol

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Donor-reactive memory T (Tm)cells mediate accelerated rejection, which is known as a barrier to the survival of transplanted organs. Selective interference with the anti-CD45RB monoclonal antibody (α-CD45RB) reliably induces donor-specific tolerance. In this study, pre-sensitization to female C57BL/6 mice with the skin of female BLAB/c mice generated a large number of Tm cells and resulted in rapid rejection of the secondly transplanted allografts. α-CD45RB did induce the tolerance to skin allograft primarily transplanted but failed to induce tolerance in the pre-sensitized mice. Donor-specific spleen cell transfusion (DST) alone also failed to induce the tolerance in the pre-sensitized recipients. Interestingly, combination of α-CD45RB with DST inhibited the rejection induced by memory T cells in the pre-sensitized mice. CD25+ T-cell depletion in α-CD45RB combined with DST therapy recipients could prevent skin allograft tolerance from establishing. In addition, adoptive transfer of donor-primed memory T cells into the tolerant recipients markedly broke the established tolerance. Our findings indicate that α-CD45RB and DST can synergistically inhibit the accelerated rejection mediated by memory T cells and induce long-term skin allograft acceptance in mice.

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Anti‐CD45RB and donor‐specific spleen cells transfusion inhibition allograft skin rejection mediated by memory T cells

Jian

et al. 2016

Immunol Cell Biol

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“…Preclinical studies demonstrated promising data on the replacement of calcineurin inhibitors (CNI) by less nephrotoxic immunosuppressive drugs, such as mTOR inhibitors or costimulatory blockade, or even induction of tolerance. Most promising results came from T(/B)-cell depletion and costimulatory blockade, alone or in combination with hematopoetic stem cell transplantation (2)(3)(4)(5)(6).…”

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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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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“…For this reason it is necessary to better know the mechanisms of chronic graft dysfunctions that could represent future treatments target to prevent graft loss [88]. In this regard, a sinergism between mesenchimal stem cells and immunosuppressive drugs should be investigated [89].…”

Section: Unresolved Issues and Future Prospectivesmentioning

confidence: 99%

Repeated immune and non immune insults to the graft after heart transplantation

et al. 2011

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Combination of monoclonal antibodies with DST inhibits accelerated rejection mediated by memory T cells to induce long-lived heart allograft acceptance in mice

Cited by 5 publications

References 31 publications

Anti‐CD45RB and donor‐specific spleen cells transfusion inhibition allograft skin rejection mediated by memory T cells

Anti‐CD45RB and donor‐specific spleen cells transfusion inhibition allograft skin rejection mediated by memory T cells

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

Repeated immune and non immune insults to the graft after heart transplantation

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