Pre-transplant Thymic Function Predicts Is Associated With Patient Death After Kidney Transplantation

Courivaud, Cécile; Bamoulid, Jamal; Crépin, Thomas; Gaiffe, Émilie; Laheurte, Caroline; Saas, Philippe; Ducloux, Didier

doi:10.3389/fimmu.2020.01653

Cited by 11 publications

(12 citation statements)

References 29 publications

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“…Especially CCR7 + RTE T cell differentiation via CD31 + memory T cells into CD31 - memory T cells appeared to be effectively blocked by the immunosuppressive therapy. Additionally, kidney failure comes along with a thymus involution and thus reduced distribution of CCR7 + RTEs ( 8 ). This dysfunction may be restored after kidney transplantation, which is another possible explanation for the markedly increased frequencies of CCR7 + RTE Tregs in kidney transplant patients.…”

Section: Discussionmentioning

confidence: 99%

Chronic Kidney Failure Provokes the Enrichment of Terminally Differentiated CD8+ T Cells, Impairing Cytotoxic Mechanisms After Kidney Transplantation

et al. 2022

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Chronic kidney failure (KF) provokes the development of immune senescent CD8+ cytotoxic T cells, affecting the occurrence of graft rejection, viral infections, and malignancies after kidney transplantation. In this study, we analyzed the impact of KF, subsequent dialysis treatment, and kidney transplantation on the differentiation of CD8+CD31+CD45RA+CCR7+ recent thymic emigrant (CCR7+ RTE) Tregs/Tresps into CD8+CD31-CD45RA- memory (CD31- memory) Tregs/Tresps and its effect on the release of cytokines, Fas receptor, Fas ligand as well as cytotoxic mediators by naïve, central memory (CM), effector memory (EM), and terminally differentiated effector memory (TEMRA) Tresps. We found that normal age-dependent differentiation of CD8+ Tregs/Tresps generally differs in the way that TEMRA cells only arise in Tresps. Compared to healthy controls, KF patients revealed an age-independently decreased frequency of CCR7+ RTE Tregs/Tresps, but increased frequencies of CCR7+ MN Tregs/Tresps and CD31- memory Tregs/Tresps, suggesting an increased differentiation via CD31+CD45RA- memory (CD31+ memory) Tregs/Tresps into CD31- memory Tregs/Tresps. Intensified differentiation via CD31+ memory Tresps increased the emergence of apoptosis-resistant CM Tresps with strong Fas ligand-mediated cytotoxicity. CCR7+ RTE Tresp proliferation generated TEMRA Tresps, secreting high levels of cytotoxic mediators. In dialysis and transplant patients, CD31+ TEMRA Tregs/Tresps accumulated, proposing an impaired CCR7+ RTE Treg/Tresp differentiation via CD31+ memory Tregs/Tresps into CD31- memory Tregs/Tresps. Increased percentages of CD31- TEMRA Tresps, but not of CD31- TEMRA Tregs, were observed in all patient groups, indicating impaired proliferation of CCR7+ RTE Tresps, but not of CCR7+ RTE Tregs, into CD31- memory Tregs/Tresps. In transplant patients, CCR7+ RTE Tregs accumulated, while frequencies of CCR7+ RTE Tresps were decreased, suggesting that the immunosuppressive therapy only prevented excessive CCR7+ RTE Treg differentiation but not that of CCR7+ RTE Tresps. Presumably, this caused the accumulation of TEMRA Tresps with decreased release of cytotoxic mediators, such as perforin. In conclusion, we propose that chronic KF affects both the differentiation of CD8+ Tregs and CD8+ Tresps. However, the immunosuppressive therapy after transplantation may successfully prevent excessive Treg differentiation, but not as suffciently that of Tresps. Therefore, the risk for graft rejection may be reduced, while the susceptibility for infections and malignancies may be increased in these patients.

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Section: Discussionmentioning

confidence: 99%

Chronic Kidney Failure Provokes the Enrichment of Terminally Differentiated CD8+ T Cells, Impairing Cytotoxic Mechanisms After Kidney Transplantation

et al. 2022

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“…Additionally, progressive thymic involution is a predominant characteristic of ESRD-associated immune senescence. Courivaud et al assessed the thymic function before transplantation via recent thymic emigrants (RTE) and found that lower levels of RTE were strongly correlated with poor outcomes in renal allograft recipients [ 15 ]. A recent single-cell transcriptome study showed that among ESRD patients there were a marked rise in inflammation reaction, complement cascade, and cell metabolism, and a significant decline in regulating the progression of immune cell cycle in related cell-types [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

“…After renal transplantation, with the recovery of renal function and the reduction of toxins, the immune function of the renal allograft recipients can be gradually rebuilt and repaired [ 13 , 14 ]. Pre-transplant immune function in patients with ESRD can clearly affect post-operative outcome and survival [ 15 ]. Therefore, we speculated that there might be links between pre-transplant PLS and post-operative outcomes, especially the incidence and progression of pneumonia.…”

Section: Introductionmentioning

confidence: 99%

Pre-Transplant Peripheral Lymphocyte Subsets Predict Pneumonia After Renal Transplantation

Zhuang¹,

Yang²,

Liu³

et al. 2022

Ann Transplant

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Background Kidney transplantation (KTx) has been considered as the most effective therapeutic method for end-stage renal disease. Immune monitoring of peripheral lymphocyte subsets (PLS) reflects the real immune status and has been used for diagnosis of pneumonia after KTx. We aimed to investigate the association between pre-transplant PLS and pneumonia in renal allograft recipients. Material/Methods A total of 152 patients receive donation after citizen’s death (DCD) kidney allografts in our center between January 2018 and December 2019. Among them, 114 patients were enrolled in our study based on inclusion and exclusion criteria. During the first-year follow-up after KTx, 32 recipients developed pneumonia, and the other 82 recipients did not (stable group). The pre-clinical information and PLS (including the percentages and absolute numbers (Ab No.) of peripheral T, B, and NK cells, as well as CD4/CD8 ratio) results in these 2 groups were calculated by the Mann-Whitney test and receiver operating curve (ROC) analysis. Univariate and multivariate logistic regression analyses were employed to identify risk factors. Results Compared to the stable group, the Ab No. of CD3+, CD8+, and CD4+ T cells, as well as B cells and NK cells, were notably reduced in the pneumonia patients. The area under the curve (AUC) of CD3+ T cell Ab No. was 0.7022. Multivariate analysis demonstrated that pre-transplant B cell Ab No. was the independent risk factor for pneumonia progression after KTx (OR=0.353, P =0.037). Conclusions Pre-transplant Ab No. of PLS were closely related to pneumonia after KTx. Monitoring pre-transplant PLS could provide more timely and effective prevention and therapy for post-operative pneumonia after KTx.

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“…In this investigation, the TREC copy number in 1×10 6 PBMCs was calculated by dividing the mean TREC copy number by half the TCRAC copy number, since each cell has two copies, one for each chromosome. TREC does not replicate itself during cell division, however, TCRAC is passed to the newly created cell (15).…”

Section: Methodsmentioning

confidence: 99%

“…Lymphocyte kinetics have an impact on the tolerance of transplanted tissue (3). The process of graft rejection or tolerance is dependent on the direct or indirect presentation of graft antigens to alloreactive T-lymphocytes (4)(5)(6). Pre-Tlymphocytes originating from the bone marrow enter the thymus via the blood and go through the stages of selection and maturation into T-lymphocytes.…”

mentioning

confidence: 99%

Monitoring T-Cell Kinetics in the Early Recovery Period of Lung Transplantation Cases by Copy Number Levels of T-Cell Receptor Excision Circle

Akdeniz

Akbulut

Vayvada

et al. 2023

In Vivo

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Background/Aim: Lung transplantation is a lifesaving procedure for patients with end-stage lung diseases. T-Cell receptor excision circle (TREC) is circular DNA produced during T-cell receptor gene rearrangement in the thymus and indicates naive T-cell migration from the thymus. Therefore, its levels represent thymic T-cell output. Post-transplant lymphocyte kinetics correlate with graft tolerance. The aim of this study was to investigate T-lymphocyte kinetics in the early recovery period after lung transplantation. For this purpose, copy numbers of TREC were determined in patients with a lung transplant. In addition, TREC copy numbers were evaluated according to age, diagnosis and the forced expiratory volume in 1 second (FEV1) of lung transplant patients. Materials and Methods: Peripheral blood samples were taken from patients aged 23 to 59 years who underwent lung transplantation at the Thoracic Surgery Clinic, Kartal-Koşuyolu High Specialization Educational and Research Hospital. This study included peripheral blood samples from 11 lung transplant patients (comprising four with chronic obstructive pulmonary disease, three with idiopathic pulmonary fibrosis, one with cystic fibrosis, one with silicosis and two with bronchiectasis; three females in total). Samples were taken at three different timepoints: Before transplant, and 24 hours and 7 days post transplant. TREC copy numbers were analyzed with real time reverse transcriptase-polymerase chain reaction. Results: Post-transplant TREC numbers and density values were higher compared to pre-transplant values, although these differences were statistically insignificant. TREC copy numbers were found to be significantly higher in patients younger than 45 years compared to patients older than 45 years. At 24 hours after the transplant, the average TREC copy number/peripheral blood mononuclear cells of the cases with an FEV1 value of or below 50% was found to be statistically significantly higher than that of cases with an FEV1 value above 50% (p=0.046). There was no statistically significant difference in TREC copy numbers between male and female patients or by diagnostic group. Conclusion: TREC copy numbers can be evaluated as a prognostic marker for lung transplantation. There is a need for multicenter studies with more patients.

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Pre-transplant Thymic Function Predicts Is Associated With Patient Death After Kidney Transplantation

Cited by 11 publications

References 29 publications

Chronic Kidney Failure Provokes the Enrichment of Terminally Differentiated CD8+ T Cells, Impairing Cytotoxic Mechanisms After Kidney Transplantation

Chronic Kidney Failure Provokes the Enrichment of Terminally Differentiated CD8+ T Cells, Impairing Cytotoxic Mechanisms After Kidney Transplantation

Pre-Transplant Peripheral Lymphocyte Subsets Predict Pneumonia After Renal Transplantation

Monitoring T-Cell Kinetics in the Early Recovery Period of Lung Transplantation Cases by Copy Number Levels of T-Cell Receptor Excision Circle

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