Induction of bona fide regulatory T cells after liver transplantation - the potential influence of polyclonal antithymocyte globulin

Stauch, Diana; Yahyazadeh, Ali; Bova, Roberta; Melloh, Götz-Christian; Füldner, Arne; Baron, Udo; Olek, Sven; Göldner, Katrin; Weiß, Sascha; Pratschke, Johann; Kotsch, Katja

doi:10.1111/j.1432-2277.2011.01405.x

Cited by 6 publications

(5 citation statements)

References 32 publications

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“…Immunomodulatory effects of ATGs might also add to the benefit of an ATG treatment. Therefore, the capability of ATG to elicit FOXP3 expression along with a regulatory phenotype in human T cells has attracted the attention of clinicians as well as of basic immunologists . However, in human T cells, FOXP3 expression is not restricted to a regulatory phenotype, since this transcription factor is also induced in nonregulatory T cells (non‐Tregs) upon activation .…”

Section: Discussionmentioning

confidence: 99%

A Comprehensive and Quantitative Analysis of the Major Specificities in Rabbit Antithymocyte Globulin Preparations

Popow

Leitner

Grabmeier‐Pfistershammer

et al. 2013

American Journal of Transplantation

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Antithymocyte globulin (ATG) preparations are used for treatment and prevention of graft rejection episodes, graft versus host disease and aplastic anemia. The immunomodulatory and immuosuppressive properties of ATGs are mediated by their interaction with a large variety of antigens expressed on immune and nonimmune cell populations. We have conducted a comprehensive analysis on antibody specificities contained in rabbit ATGs in clinical use, ATG-Fresenius (ATG-F) and Thymoglobulin (THG). We have used retroviral expression cloning to identify novel ATG antigens and demonstrate that together with ATG antigens described earlier, these molecules account for the majority of ATG antibodies directed to human cells. Moreover, we have employed cell lines engineered to express antigens at high levels to quantify the antibodies directed to each ATG antigen. We have used cell lines expressing the T cell receptor complex, CD2 and CD28 to remove antibodies to these antigens from ATG preparations and demonstrate that this treatment abrogated the ability of ATGs to induce activation and forkhead box P3 expression in T cells. Comprehensive information and differences on the antigens targeted by ATG-F and THG as well as novel approaches to assess their functional properties are the basis for a better understanding of their immunomodulatory capacities and might eventually translate into improved ATGbased regimen.

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Section: Discussionmentioning

confidence: 99%

A Comprehensive and Quantitative Analysis of the Major Specificities in Rabbit Antithymocyte Globulin Preparations

Popow

Leitner

Grabmeier‐Pfistershammer

et al. 2013

American Journal of Transplantation

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“…This is supported by the fact that the use of induction agents has increased over recent years as reflected by the finding that in 2013 more than 89% of kidney transplants in the United States were performed with induction therapy (21). As we and others have already illustrated that rATG induction therapy is also a safe and reasonable approach in liver transplantation (22, 23), we explored the potential for perfusing donor kidneys peri-operatively with ATLG in order to ameliorate IRI in a prospective, single-center, single-blinded, randomized placebo-controlled trial.…”

Section: Introductionmentioning

confidence: 99%

Graft Pre-conditioning by Peri-Operative Perfusion of Kidney Allografts With Rabbit Anti-human T-lymphocyte Globulin Results in Improved Kidney Graft Function in the Early Post-transplantation Period—a Prospective, Randomized Placebo-Controlled Trial

et al. 2018

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Introduction: Although prone to a higher degree of ischemia reperfusion injury (IRI), the use of extended criteria donor (ECD) organs has become reality in transplantation. We therefore postulated that peri-operative perfusion of renal transplants with anti-human T-lymphocyte globulin (ATLG) ameliorates IRI and results in improved graft function.Methods: We performed a randomized, single-blinded, placebo-controlled trial involving 50 kidneys (KTx). Prior to implantation organs were perfused and incubated with ATLG (AP) (n = 24 kidney). Control organs (CP) were perfused with saline only (n = 26 kidney). Primary endpoint was defined as graft function reflected by serum creatinine at day 7 post transplantation (post-tx).Results: AP-KTx recipients illustrated significantly better graft function at day 7 post-tx as reflected by lower creatinine levels, whereas no treatment effect was observed after 12 months surveillance. During the early hospitalization phase, 16 of the 26 CP-KTx patients required dialysis during the first 7 days post-tx, whereas only 10 of the 24 AP-KTx patients underwent dialysis. No treatment-specific differences were detected for various lymphocytes subsets in the peripheral blood of patients. Additionally, mRNA analysis of 0-h biopsies post incubation with ATLG revealed no changes of intragraft inflammatory expression patterns between AP and CP organs.Conclusion: We here present the first clinical study on peri-operative organ perfusion with ATLG illustrating improved graft function in the early period post kidney transplantation.Clinical Trial Registration: www.ClinicalTrials.gov, NCT03377283

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“…65 The mechanism by which antithymocyte globulin induces expansion of T-regs is conversion of CD4 + CD25 -cells to CD4 + CD25 + cells. 66 Antithymocyte globulin in humans depletes T cells; thus, it may be useful for lymphodepletion before T-reg therapy where it can increase the T-reg/T effector ratio.…”

Section: Effects Of Immunosuppressive Drugs On T-regsmentioning

confidence: 99%

Regulatory T Cells as a Therapeutic Tool To Induce Solid-Organ Transplant Tolerance: Current Clinical Experiences

Nikoueinejad¹,

Sharif²,

Amirzargar³

et al. 2013

Exp Clin Transplant

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Long-term tolerance is potentially an ideal in organ transplant. Achieving this leads us to eliminate immunosuppressive therapies and their associated side effects. Although most succession in this field belongs to mixed chimerism methods of tolerance induction, regulatory T cells and (T-reg)-based methods also have been demonstrated to prevent organ rejection and lead to transplant tolerance through different mechanisms. In contrast to chimeric protocols (which require bone marrow transplant), T-reg-mediated protocols do not aggressively manipulate blood and the immune system. Most treatment has been done for graft-versus-host disease after hematopoietic stem cell transplant. This review describes different types and mechanisms of action and clinical strategies using T-regs to induce transplant tolerance.

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Induction of bona fide regulatory T cells after liver transplantation - the potential influence of polyclonal antithymocyte globulin

Cited by 6 publications

References 32 publications

A Comprehensive and Quantitative Analysis of the Major Specificities in Rabbit Antithymocyte Globulin Preparations

A Comprehensive and Quantitative Analysis of the Major Specificities in Rabbit Antithymocyte Globulin Preparations

Graft Pre-conditioning by Peri-Operative Perfusion of Kidney Allografts With Rabbit Anti-human T-lymphocyte Globulin Results in Improved Kidney Graft Function in the Early Post-transplantation Period—a Prospective, Randomized Placebo-Controlled Trial

Regulatory T Cells as a Therapeutic Tool To Induce Solid-Organ Transplant Tolerance: Current Clinical Experiences

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