Utility of CD127 combined with FOXP3 for identification of operational tolerance after liver transplantation

Nafady-Hego, Hanaa; Liu, Ying; Ohe, Hidenori; Elgendy, Hamed; Zhao, Xiangdong; Sakaguchi, Shimon; Bishop, G. Alex; Koshiba, T

doi:10.1016/j.trim.2016.04.005

Cited by 13 publications

(18 citation statements)

References 37 publications

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“…Of the 11 completed ISW studies, six (three prospective and three retrospective studies) reported on pediatric and five (all prospective) on adult LT recipient cohorts (Tables S3, S6, S7). Three monocenter pediatric ISW studies were from Kyoto (Japan), 17,18,20,27 Tochigi (Japan), 22,33 and Taipei (Taiwan) 23 and three multicenter pediatric ISW studies 14,31,35 from North American liver transplantation units. Four monocenter adult ISW studies were from Chicago (US), 34 Murcia (Spain) 13,16,21,24,29 [two studies], and Pamplona (Spain) 26,28 [one report 32 integrated the clinical parameters from one Pamplona and three Murcia trials], and one multicenter adult ISW study 15,19,25,30 analyzed trial data from Barcelona (Spain), Rome (Italy), and Leuven (Belgium).…”

Section: Results Of the Search And Study Characteristicsmentioning

confidence: 99%

Clinical parameters and biomarkers predicting spontaneous operational tolerance after liver transplantation: A scoping review

Appenzeller-Herzog

Hartleif

Vionnet

2021

American Journal of Transplantation

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The introduction of potent pharmacological immunosuppression (IS) regimens in the late 1970s, in particular calcineurin inhibitors (CNIs), kick-started the medical and surgical success story of solid organ transplantation (SOT). While preventing acute and chronic rejection, these treatments are directly or indirectly responsible for various complications including recurrent or de novo malignancies,

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Section: Results Of the Search And Study Characteristicsmentioning

confidence: 99%

Clinical parameters and biomarkers predicting spontaneous operational tolerance after liver transplantation: A scoping review

Appenzeller-Herzog

Hartleif

Vionnet

2021

American Journal of Transplantation

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“…16 We have also tracked donor-specific TCRs in the cir- phenomena may develop over longer periods in most patients who achieve tolerance. Regulatory T cells (Tregs) are enriched in tolerant liver transplant recipients, [23][24][25] and donor-specific Treg infusion promoted tolerance in 7 of 10 liver transplant recipients. 26 In contrast to the sequence proposed here for liver allograft tolerance, we have proposed a sequential Treg-dependent/deletion-dependent model to explain the tolerance observed in CKBMT recipients with transient chimerism.…”

Section: Discussionmentioning

confidence: 99%

“…Regulatory T cells (Tregs) are enriched in tolerant liver transplant recipients,[23][24][25] and donor-specific Treg infusion promoted tolerance in 7 of 10 liver transplant recipients 26. Regulatory T cells (Tregs) are enriched in tolerant liver transplant recipients,[23][24][25] and donor-specific Treg infusion promoted tolerance in 7 of 10 liver transplant recipients 26.…”

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confidence: 99%

Deletion of donor-reactive T cell clones after human liver transplant

Savage

Shonts

Lau

et al. 2020

American Journal of Transplantation

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| INTRODUC TI ONLiver transplantation has been associated with relatively high rates of successful immunosuppression withdrawal in recipients who have been free of rejection for years. 1,2 Despite T cell infiltration associated with hepatitis C virus (HCV) and recurrent HCV posttransplant, 3 a subset of HCV-infected liver transplant recipients have successfully achieved tolerance. 4Spontaneous liver allograft tolerance occurs in rodent models across major histocompatibility complex barriers 5 and is associated with donor-specific tolerance to subsequent skin 6 or cardiac allografts. 7 Moreover, cotransplantation of liver allografts in humans We recently developed a high throughput T cell receptor β chain (TCRβ) sequencing-based approach to identifying and tracking donor-reactive T cells. To address the role of clonal deletion in liver allograft tolerance, we applied this method in samples from a recent randomized study, ITN030ST, in which immunosuppression withdrawal was attempted within 2 years of liver transplantation. We identified donor-reactive T cell clones via TCRβ sequencing following a pre-transplant mixed lymphocyte reaction and tracked these clones in the circulation following transplantation in 3 tolerant and 5 non-tolerant subjects. All subjects showed a downward trend and significant reductions in donor-reactive TCRβ sequences were detected post-transplant in 6 of 8 subjects, including 2 tolerant and 4 non-tolerant recipients. Reductions in donor-reactive TCRβ sequences were greater than those of all other TCRβ sequences, including 3rd party-reactive sequences, in all 8 subjects, demonstrating an impact of the liver allograft after accounting for repertoire turnover. Although limited by patient number and heterogeneity, our results suggest that partial deletion of donor-reactive T cell clones may be a consequence of liver transplantation and does not correlate with success or failure of early immunosuppression withdrawal. These observations underscore the organ-and/or protocol-specific nature of tolerance mechanisms in humans. K E Y W O R D Sbasic (laboratory) research/science, immunobiology, liver transplantation/hepatology, monitoring: immune, T cell biology, tolerance

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“…The constant finding that, among the in vivo evaluated Treg subpopulations, only CD4 + CD25 high CD127 low cells were protective against CLAD and mortality, underlined their role for future cell‐based therapies against CLAD. The CD127 (IL‐7 receptor) antigen is considered the most reliable marker for Treg isolation and the majority of these cells are FoxP3+ too . Instead, the FoxP3 antigen alone cannot be used for Treg isolation for cell therapy, technically, because it is expressed intracellularly.…”

Section: Discussionmentioning

confidence: 99%

Increased frequency of CD4⁺CD25^highCD127^lowT cells early after lung transplant is associated with improved graft survival – a retrospective study

et al. 2020

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In this retrospective study, we analyzed the presence of any association of three CD4 + CD25 high regulatory T-cell subpopulations at 3 weeks after lung transplantation with the later incidence of chronic lung allograft dysfunction and graft survival. Among lung-transplanted patients between January 2009 and April 2018, only patients with sufficient T-cell measurements at 3 weeks after transplantation were included into the study. Putative regulatory T cells were defined as CD4 + CD25 high T cells, detected in peripheral blood and further analyzed for CD127 low , FoxP3 + , and CD152 + using fluorescence-activated cell sorting (FACS) analysis. Associations of regulatory T cells with chronic lung allograft dysfunction (CLAD) and graft survival were evaluated using Cox analysis. During the study period, 724 (71%) patients were included into the study. Freedom from chronic lung allograft dysfunction (CLAD) and graft survival amounted to 66% and 68% at 5 years. At the multivariable analysis, increasing frequencies of CD127 low were associated with better freedom from CLAD (hazard ratio for each 1% increase of %CD127 low , HR = 0.989, 95% CI = 0.981-0.996, P = 0.003) and better graft survival (HR = 0.991, 95% CI = 0.984-0.999, P = 0.026). A higher frequency of CD127 low regulatory T cells in peripheral blood early after lung transplantation estimated a protective effect against chronic lung allograft dysfunction, mortality, and re-transplantation.

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Utility of CD127 combined with FOXP3 for identification of operational tolerance after liver transplantation

Cited by 13 publications

References 37 publications

Clinical parameters and biomarkers predicting spontaneous operational tolerance after liver transplantation: A scoping review

Clinical parameters and biomarkers predicting spontaneous operational tolerance after liver transplantation: A scoping review

Deletion of donor-reactive T cell clones after human liver transplant

Increased frequency of CD4⁺CD25^highCD127^lowT cells early after lung transplant is associated with improved graft survival – a retrospective study

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Utility of CD127 combined with FOXP3 for identification of operational tolerance after liver transplantation

Cited by 13 publications

References 37 publications

Clinical parameters and biomarkers predicting spontaneous operational tolerance after liver transplantation: A scoping review

Clinical parameters and biomarkers predicting spontaneous operational tolerance after liver transplantation: A scoping review

Deletion of donor-reactive T cell clones after human liver transplant

Increased frequency of CD4+CD25highCD127lowT cells early after lung transplant is associated with improved graft survival – a retrospective study

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Increased frequency of CD4⁺CD25^highCD127^lowT cells early after lung transplant is associated with improved graft survival – a retrospective study