Faculty Opinions recommendation of Uptake of donor lymphocytes treated with 8-methoxypsoralen and ultraviolet A light by recipient dendritic cells induces CD4+CD25+Foxp3+ regulatory T cells and down-regulates cardiac allograft 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.

Download Full-text

Intralipid ® attenuates acute cardiac allograft rejection in relation to promoting CD4 + CD25 + Foxp3 + regulatory T-cells and inhibiting toll-like receptor 4 expression

Transplantation Reports ◽

10.1016/j.tpr.2017.05.001 ◽

2017 ◽

Vol 2 (1) ◽

pp. 1-9

Author(s):

Q. Ye ◽

L. Liu ◽

Y.L. Wu ◽

F. Yeh ◽

W.F. Li ◽

...

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Allograft Rejection ◽

Cardiac Allograft ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Cardiac Allograft Rejection

Download Full-text

Foxp3-expressing Regulatory T Cells Expanded With CD28 Superagonist Antibody Can Prevent Rat Cardiac Allograft Rejection

The Journal of Heart and Lung Transplantation ◽

10.1016/j.healun.2008.01.004 ◽

2008 ◽

Vol 27 (4) ◽

pp. 362-371 ◽

Cited By ~ 21

Author(s):

Yusuke Kitazawa ◽

Masayuki Fujino ◽

Takatoshi Sakai ◽

Haruhito Azuma ◽

Hiromitsu Kimura ◽

...

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Allograft Rejection ◽

Cardiac Allograft ◽

Cardiac Allograft Rejection

Download Full-text

Aspirin Attenuates Cardiac Allograft Rejection by Inhibiting the Maturation of Dendritic Cells via the NF-κB Signaling Pathway

Frontiers in Pharmacology ◽

10.3389/fphar.2021.706748 ◽

2021 ◽

Vol 12 ◽

Author(s):

Xi Zhang ◽

Aie Chang ◽

Yanqiang Zou ◽

Heng Xu ◽

Jikai Cui ◽

...

Keyword(s):

Immune Response ◽

T Cells ◽

Dendritic Cells ◽

Signaling Pathway ◽

Inflammatory Cytokines ◽

Allograft Rejection ◽

Cardiac Allograft ◽

Cardiac Allograft Rejection ◽

Pro Inflammatory Cytokines

Background: Dendritic cells (DCs) serve as an important part of the immune system and play a dual role in immune response. Mature DCs can initiate immune response, while immature or semi-mature DCs induce immune hyporesponsiveness or tolerance. Previous studies have shown that aspirin can effectively inhibit the maturation of DCs. However, the protective effect of aspirin on acute cardiac allograft rejection has not been studied. The aim of this study was to elucidate the effect of aspirin exert on allograft rejection.Methods: The model of MHC-mismatched (BALB/c to B6 mice) heterotopic heart transplantation was established and administered intraperitoneal injection with aspirin. The severity of allograft rejection, transcriptional levels of cytokines, and characteristics of immune cells were assessed. Bone marrow-derived dendritic cells (BMDCs) were generated with or without aspirin. The function of DCs was determined via mixed lymphocyte reaction (MLR). The signaling pathway of DCs was detected by Western blotting.Results: Aspirin significantly prolonged the survival of cardiac allograft in mouse, inhibited the production of pro-inflammatory cytokines and the differentiation of effector T cells (Th1 and Th17), as well as promoted the regulatory T cells (Treg). The maturation of DCs in the spleen was obviously suppressed with aspirin treatment. In vitro, aspirin decreased the activation of NF-κB signaling of DCs, as well as impeded MHCII and co-stimulatory molecules (CD80, CD86, and CD40) expression on DCs. Moreover, both the pro-inflammatory cytokines and function of DCs were suppressed by aspirin.Conclusion: Aspirin inhibits the maturation of DCs through the NF-κB signaling pathway and attenuates acute cardiac allograft rejection.

Download Full-text