scholarly journals Isolation and expansion of thymus‐derived regulatory T cells for use in paediatric heart transplant patients

2021 ◽  
Author(s):  
Marco Romano ◽  
Monica Sen ◽  
Cristiano Scottà ◽  
Rowa Y. Alhabbab ◽  
Andres Rico‐Armada ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Heart Transplant ◽  
Transplant Patients

scholarly journals Specific recruitment of CD4+CD25++ regulatory T cells into the allograft in heart transplant recipients

2007 ◽  
Vol 292 (5) ◽  
pp. H2425-H2431 ◽  
Author(s):  
Caroline Schmidt-Lucke ◽  
Alexandra Aicher ◽  
Paola Romagnani ◽  
Björn Gareis ◽  
Sergio Romagnani ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Heart Transplant ◽  
Cell Types ◽  
Systemic Circulation ◽  
Cardiac Allograft ◽  
Transplant Recipients ◽  
Activated T Cells ◽  
Transplant Patients ◽  
Heart Transplant Recipients

Regulatory T cells (Treg) migrate into allografts and induce tolerance of the graft. Immunosuppressive Treg are found among CD4+CD25++ T cells and specifically express the forkhead/winged transcription factor FOXP3. We hypothesized that activated T cells and Treg might modulate the ongoing inflammation of the cardiac allograft (CA) and that the chronic inflammatory environment might influence the balance between these distinct cell types. We therefore quantified levels of activated T cells and CD4+CD25++ Treg in the cardiac and systemic circulation in heart transplant recipients. To determine the influence of the allograft passage on these cells, transcardiac gradients were evaluated in CA recipients ( n = 22) compared with controls ( n = 18). Systemic levels of circulating Treg were significantly lower in CA recipients (8.9 ± 1.3 μl) compared with controls (15.8 ± 1.6 μl; P = 0.002). Similarly, the proportion of Treg related to the total leukocyte number was significantly lower in CA recipients ( P < 0.01). In contrast, systemic levels of circulating activated CD4+ T cells and of circulating plasmacytoid dendritic cells were similar in both groups. In transplant patients, numbers of Treg significantly decreased during transcardiac passage (3.0 ± 0.3 to 2.4 ± 0.3% of CD4+ T cells, P < 0.01), and FOXP3+ T cells invaded into the allograft. In contrast, numbers of activated CD4+ T cells increased during passage through the allograft, even in the presence of effective immunosuppression. In conclusion, numbers of circulating immunosuppressive Treg are reduced in transplant recipients. Recruitment of Treg into the cardiac allograft during transcoronary passage may induce graft tolerance during subclinical inflammation potentially influencing allograft vasculopathy.

scholarly journals MiR-146a regulates regulatory T cells to suppress heart transplant rejection in mice

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jian Lu ◽  
Weiwei Wang ◽  
Peiyuan Li ◽  
Xiaodong Wang ◽  
Chao Gao ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Heart Transplant ◽  
Transplant Rejection ◽  
Mouse Heart ◽  
Allograft Survival ◽  
Treg Function ◽  
Ifn Γ ◽  
Heart Transplant Rejection

AbstractRegulatory T cells (Tregs), which characteristically express forkhead box protein 3 (Foxp3), are essential for the induction of immune tolerance. Here, we investigated microRNA-146a (miR-146a), a miRNA that is widely expressed in Tregs and closely related to their homeostasis and function, with the aim of enhancing the function of Tregs by regulating miR-146a and then suppressing transplant rejection. The effect of the absence of miR-146a on Treg function in the presence or absence of rapamycin was detected in both a mouse heart transplantation model and cell co-cultures in vitro. The absence of miR-146a exerted a mild tissue-protective effect by transiently prolonging allograft survival and reducing the infiltration of CD4+ and CD8+ T cells into the allografts. Meanwhile, the absence of miR-146a increased Treg expansion but impaired the ability of Tregs to restrict T helper cell type 1 (Th1) responses. A miR-146a deficiency combined with interferon (IFN)-γ blockade repaired the impaired Treg function, further prolonged allograft survival, and alleviated rejection. Importantly, miR-146a regulated Tregs mainly through the IFN-γ/signal transducer and activator of transcription (STAT) 1 pathway, which is implicated in Treg function to inhibit Th1 responses. Our data suggest miR-146a controls a specific aspect of Treg function, and modulation of miR-146a may enhance Treg efficacy in alleviating heart transplant rejection in mice.

scholarly journals Induction of IL-10 Suppressors in Lung Transplant Patients by CD4+25+ Regulatory T Cells through CTLA-4 Signaling

2006 ◽  
Vol 177 (8) ◽  
pp. 5631-5638 ◽  
Author(s):  
Ankit Bharat ◽  
Ryan C. Fields ◽  
Elbert P. Trulock ◽  
G. Alexander Patterson ◽  
Thalachallour Mohanakumar
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Lung Transplant ◽  
Transplant Patients

scholarly journals Evaluation of Myocardial Perfusion and Immune Cell Response in Cardiac Allograft Dysfunction of Heart-Transplant Patients

2020 ◽  
Author(s):  
Paul J. Kim ◽  
Francisco Contijoch ◽  
Gerald Morris ◽  
Darrin Wong ◽  
Patricia Nguyen
Keyword(s):  
T Cells ◽  
Myocardial Perfusion ◽  
Heart Transplant ◽  
Immune Cell ◽  
Cardiac Allograft ◽  
Normal Heart ◽  
Graft Dysfunction ◽  
Stress Myocardial Perfusion ◽  
Transplant Patients ◽  
Immune Cell Response

BackgroundWe investigated the myocardial perfusion differences and changes in immune cell response in heart-transplant patients with nonspecific graft dysfunction (NGD) compared to cardiac allograft vasculopathy (CAV) patients and normal heart-transplant patients.Methods and ResultsWe prospectively studied 17 heart-transplant patients (59.8±14.1 years, 78% male) from January to June 2016. Regadenoson stress cardiac MRI was performed in the patients and peripheral blood obtained contemporaneously to isolate peripheral blood mononuclear cells (PBMCs). Stress myocardial perfusion showed significantly decreased myocardial perfusion using maximum upslope method in NGD and CAV patients compared to normal heart-transplant patients. Myocardial scar by late gadolinium enhancement also was significantly increased in nonspecific graft dysfunction patients compared to normal. Evaluation of PBMCs by flow cytometry showed a trend towards increased activated HLA-DR+ T cells in NGD patients compared to normal. Clinical outcomes for cardiac hospitalization, allograft loss/retransplant, death were assessed at 3 years.ConclusionsNGD shows decreased stress myocardial perfusion by cardiac MRI and a trend towards increased activated T cells in PBMCs, suggestive of an immune-mediated cause for allograft dysfunction.

P761The effect of extracorporeal photopheresis on cardiac allograft rejection and on lymphocyte subclasses

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
T Teszak ◽  
A Assabiny ◽  
A Kiraly ◽  
Z Tarjanyi ◽  
N Parazs ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
B Lymphocytes ◽  
Heart Transplant ◽  
Allograft Rejection ◽  
Cytotoxic T Cells ◽  
Cardiac Allograft ◽  
Extracorporeal Photopheresis ◽  
Cardiac Allograft Rejection ◽  
Cellular Rejection

Abstract Background Cardiac allograft rejection is known to have a profound impact on graft survival and mortality after heart transplant. Previous data on the efficacy of extracorporeal photopheresis (ECP) in the management of cardiac allograft rejection is encouraging. Though, clear evidence on the exact indication and data regarding its effect on distinct lymphocyte subtypes are still lacking. Based on their cytokine production, both helper and cytotoxic T cells can differentiate into either regulatory cells participating in the suppression of rejection or into effector cells responsible for its maintenance. Regulatory T cells are essential for the termination of rejection, while B lymphocytes and natural killer (NK) cells contribute to it. Purpose We aimed to investigate the anti-rejection efficacy and the impact of ECP on peripheral blood lymphocyte subclasses in adult heart transplant recipients. Methods In a retrospective analysis of 12 consecutive patients treated with ECP for cardiac allograft rejection between 2013 and 2019, we examined the grade of rejection in endomyocardial biopsies (EMB) based on the International Society for Heart and Lung Transplantation classification. We analysed the absolute counts and the percentages of helper, cytotoxic and regulatory T cells, B lymphocytes and NK cells with fluorescence activated cell sorting. Measurements were performed both before and after the ECP treatment period. Data values were given as either mean±standard deviation or median [min–max]. Results The patients underwent 26 [2–39] ECP treatments in addition to standard immunosuppressant therapy. Whereas grade 2R cellular rejection was detected in 83% of the cases prior to initiating ECP, none of the examined EMB specimen revealed rejection greater than grade 1R cellular rejection post ECP therapy. The average grade of cellular rejection improved significantly (1.25±0.45 vs. 0.50±0.53; p=0.022). The absolute count and the percentage of helper T cells increased significantly post ECP therapy (0.34 G/l±0.26 G/l vs. 0.51 G/l±0.39 G/l; p=0.018 and 3.43%±2.24% vs. 5.98%±3.64%; p=0.017, respectively). There was also a significant rise in the percentage of cytotoxic T cells (2.33%±1.46% vs. 4.16±2.98%; p=0.027). We noticed an almost significant twofold increase in the percentage of regulatory T cells on completion of the ECP therapy (0.20%±0.22% vs. 0.37%±0.20%; p=0.060). Neither B lymphocyte nor NK cell counts revealed any significant changes. Conclusion ECP was effective in reducing the severity of cardiac allograft rejection episodes. The significant decrease in rejection rates might be indicative of the predominance of anti-inflammatory helper and cytotoxic T cell subpopulations and the increase of regulatory T cell count post ECP therapy. However, discussion of the results are limited by small sample size and the effect of medical therapy on the lymphocytes.

scholarly journals 24 EBV-specific CD8+T cells in pediatric heart transplant patients

2006 ◽  
Vol 10 ◽  
pp. S13
Author(s):  
C. Macedo ◽  
I. Popescu ◽  
Y. Hua ◽  
D. Rowe ◽  
S. Webber ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Heart Transplant ◽  
Transplant Patients ◽  
Pediatric Heart Transplant

Two-year follow-up of a prospective study of circulating regulatory T cells in renal transplant patients

2009 ◽  
Vol 24 (3) ◽  
pp. 386-393 ◽  
Author(s):  
David San Segundo ◽  
Gema Fernández-Fresnedo ◽  
Juan C. Ruiz ◽  
Emilio Rodrigo ◽  
María J. Benito ◽  
...  
Keyword(s):  
T Cells ◽  
Renal Transplant ◽  
Regulatory T Cells ◽  
Prospective Study ◽  
Transplant Patients ◽  
Renal Transplant Patients ◽  
A Prospective Study

scholarly journals The Presence of a Marked Imbalance Between Regulatory T Cells and Effector T Cells Reveals That Tolerance Mechanisms Could Be Compromised in Heart Transplant Children

2021 ◽  
Vol 7 (5) ◽  
pp. e693
Author(s):  
Esther Bernaldo-de-Quirós ◽  
Jacobo López-Abente ◽  
Manuela Camino ◽  
Nuria Gil ◽  
Esther Panadero ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Heart Transplant ◽  
Effector T Cells ◽  
Tolerance Mechanisms

scholarly journals The impact of induction therapy on the homeostasis and function of regulatory T cells in kidney transplant patients

2014 ◽  
Vol 29 (8) ◽  
pp. 1587-1597 ◽  
Author(s):  
A. P. Bouvy ◽  
M. Klepper ◽  
M. M. L. Kho ◽  
K. Boer ◽  
M. G. H. Betjes ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Kidney Transplant ◽  
Induction Therapy ◽  
Transplant Patients ◽  
Kidney Transplant Patients ◽  
And Function ◽  
The Impact
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