Differential depletion of total T cells and regulatory T cells and prolonged allotransplant survival in CD3Ɛ humanized mice treated with polyclonal anti human thymocyte globulin

Buszko, Maja; Cardini, Benno; Oberhuber, Rupert; Oberhuber, Lukas; Jakic, Bojana; Beierfuß, Anja; Wick, Georg; Cappellano, Giuseppe

doi:10.1371/journal.pone.0173088

Cited by 9 publications

(6 citation statements)

References 33 publications

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“…ATG is a lymphocyte-depleting polyclonal antibody that targets multiple immunological epitopes. There are several ATG preparations, which differ from regard to the source of human T cells and the inoculated animals [3,4]. Basiliximab is a monoclonal antibody that targets the interleukin-2 receptor [1–4].…”

Section: Introductionmentioning

confidence: 99%

Infectious Complications of Induction Therapies in Kidney Transplantation

et al. 2019

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Background Cytomegalovirus (CMV) and BK virus (BKV) are post-transplant opportunistic viral infections that affect patient and graft survival. This study was designed to evaluate the risk of BKV nephropathy and CMV disease in kidney transplant recipients who received induction therapy with ATG or basiliximab. Material/Methods We retrospectively analyzed information on 257 adult patients who underwent kidney transplantation between January 2007 and 2017. Patients were categorized into 3 groups according to the induction therapies . The primary endpoint was the onset of CMV disease or biopsy-confirmed BKV nephropathy. The secondary endpoints were biopsy-proven rejection episodes, graft loss, loss to follow-up, and death. Results We followed 257 patients for a median of 55.5 months. The incidence of CMV disease was significantly higher in the only ATG group compared to the group without induction treatment (p<0.001). There was no significant difference in the incidence of BKV nephropathy among groups (p>0.05). The dosage of ATG (OR, 10.685; 95% CI, 1.343 5 to 85.009; P=0.025) was independent risk factor for death. Conclusions This study demonstrated that a higher dosage of ATG in high-risk patients is associated with an increased risk of CMV disease and patient death, also, reducing the dosage may be a rational strategy for increasing graft and patient’s survival.

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Section: Introductionmentioning

confidence: 99%

Infectious Complications of Induction Therapies in Kidney Transplantation

et al. 2019

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“…A number of investigations demonstrated that the same monoclonal Abs that efficiently eliminate or inhibit effector T cells actually spare Foxp3 + Tregs, in contrast [13][14][15][16][17][18]. Similar observations were reported after treatment with anti-lymphocyte serum or anti-thymocyte globulin [28][29][30][31][32]. Consequently, Treg frequency (but not necessarily absolute numbers) increases in lymphoid organs and in the grafts, thus creating a local Treg-enriched microenvironment amenable to the induction of immune tolerance, and referring to an "immune privileged site" [33].…”

Section: Relative Role Of Foxp3 + Tregs For the Acquisition And The Mmentioning

confidence: 59%

The Concerted Action of Multiple Mechanisms to Induce and Sustain Transplant Tolerance

Chatenoud¹

2018

obm transplant

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Transplant tolerance has been achieved in experimental models using immune intervention strategies. Yet, their clinical translation remains unsuccessful and requires further optimization of immunotherapeutic regimens based on a deeper understanding of the cellular and molecular mechanisms at play in the induction and maintenance phases of immune tolerance. Intensive investigations have shed light on the tolerogenic networks underlying graft survival and have unraveled their complexity, which may depend on several parameters such as intrinsic features of the transplant itself (organs, tissues, and cells), the type of immunotherapy, and the therapeutic window used. It is now fairly well-established that Foxp3 + regulatory T lymphocytes (Tregs) play a central role in these networks. However, a wealth of evidence points to multiples mechanisms, including alloreactive T cell depletion and T cell anergy, that engage and cooperate in a timely manner in addition to Tregmediated suppression to tip the balance from rejection towards robust and sustained

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“…Kinetics of PBLS after LTx distinguished 2 consecutive phases in relationship with the immunosuppressive therapy. In the very early postoperative phase, there was not only a strong T cell depletion, as expected with the induction therapy with ATG [ 22 , 23 ], but also a decrease in NK cell counts. The impact of ATG on NK cells has already been reported in kidney transplantation [ 24 , 25 ].…”

Section: Discussionmentioning

confidence: 86%

Effect of Immunosuppression on Target Blood Immune Cells Within 1 Year After Lung Transplantation: Influence of Age on T Lymphocytes

et al. 2018

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BackgroundLymphocytes are targeted by immunosuppressive therapy in solid organ transplantation and they influence allograft outcome.Material/MethodsPeripheral blood lymphocyte subsets (PBLS) determined by flow cytometry during the first year post-transplant from patients who underwent a first lung transplantation in a French University Hospital between December 2011 and July 2013 were retrospectively analyzed according to recipient characteristics and allograft outcome.ResultsFifty-seven recipients were enrolled and 890 PBLS were collected. T lymphocytes and NK cells were rapidly decreased, below normal range, from the first postoperative days. B cells decreased more gradually, remaining within normal range, with the lowest level reached after day 100. In multivariate analysis, greater T lymphopenia was found in older recipients (−414 [−709 to −119] cells/μL, p=0.007). According to the outcome, multivariate analysis evidenced lower levels of lymphocytes when bacterial and viral infection occurred (−177 [−310 to −44] cells/μL, p=0.009 and (−601 [−984 to −218] cells/μL, p=0.002, respectively), higher CD8+ T lymphocytes with BOS (+324 [+94 to +553] cells/μL, p=0.006), and higher leukocytes with restrictive allograft syndrome (+3770 [+418 to +7122] cells/μL, p=0.028).ConclusionsAging is associated in our cohort with more severe T lymphopenia after induction therapy for lung transplantation. The analysis of leukocytes and PBLS is associated with specific profile according to the allograft outcome.

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Differential depletion of total T cells and regulatory T cells and prolonged allotransplant survival in CD3Ɛ humanized mice treated with polyclonal anti human thymocyte globulin

Cited by 9 publications

References 33 publications

Infectious Complications of Induction Therapies in Kidney Transplantation

Infectious Complications of Induction Therapies in Kidney Transplantation

The Concerted Action of Multiple Mechanisms to Induce and Sustain Transplant Tolerance

Effect of Immunosuppression on Target Blood Immune Cells Within 1 Year After Lung Transplantation: Influence of Age on T Lymphocytes

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