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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 6282

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Dr. Marcos López-Hoyos

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Guest Editor

1. Immunology Service, University Hospital Marqués de Valdecilla-IDIVAL, 39008 Santander, Spain
2. Molecular Biology Department, Universidad de Cantabria, 39005 Santander, Spain
Interests: immunology; autoimmunity; transplantation; tolerance; human pathology; biomarkers
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Special Issue Information

Dear Colleagues,

Transplant medicine is one of the most challenging and complex areas of modern medicine. The issue of transplant rejection often arises in medical management. During this time, the body develops an immune response to the transplant. Immunity is the ability of multicellular organisms to resist harmful microorganisms. The immune system has both innate and adaptive components. The innate component of the immune system generates when the body recognizes certain foreign, non-self molecules, which includes an inflammatory response and phagocytosis. Adaptive or acquired immunity is some active component produced by the host after immune response, mediated by antigen-specific lymphocytes. The advance in the knowledge of both soluble and cellular adaptive and acquired components of the immune response in the last two decades is outstanding. Their involvement in the regulation of immune response in general and in the alloimmune response in transplantation has also exploded.

This Special Issue focuses on the mechanisms of immune regulation during transplantation, from the molecular to the cellular level, which may provide new therapeutic avenues for the development of transplant rejection. We encourage authors to submit original articles, reviews and short communications related to this research topic.

Dr. Marcos López-Hoyos
Guest Editor

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Keywords

transplant medicine innate immune
adaptive immune
immune regulation
inflammatory response
phagocytosis
lymphocytes

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Published Papers (4 papers)

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Research

16 pages, 5155 KiB

Open AccessArticle

Recipient Pericardial Apolipoprotein Levels Might Be an Indicator of Worse Outcomes after Orthotopic Heart Transplantation

by Andrea Székely, Éva Pállinger, Evelin Töreki, Mandula Ifju, Bálint András Barta, Balázs Szécsi, Eszter Losoncz, Zsófia Dohy, Imre János Barabás, Annamária Kosztin, Edit I. Buzas, Tamás Radovits and Béla Merkely

Int. J. Mol. Sci. 2024, 25(3), 1752; https://doi.org/10.3390/ijms25031752 - 1 Feb 2024

Viewed by 1109

Abstract

Background: End-stage heart failure (ESHF) leads to hypoperfusion and edema formation throughout the body and is accompanied by neurohormonal and immunological alterations. Orthotopic heart transplantation (HTX) has been used as a beneficial option for ESHF. Due to the shortage of donor hearts, the ideal matching and timing of donors and recipients has become more important. Purpose: In this study, our aim was to explore the relationship between the clinical outcomes of HTX and the cytokine and apolipoprotein profiles of the recipient pericardial fluid obtained at heart transplantation after opening the pericardial sac. Materials and methods: The clinical data and the interleukin, adipokine, and lipoprotein levels in the pericardial fluid of twenty HTX recipients were investigated. Outcome variables included primer graft dysfunction (PGD), the need for post-transplantation mechanical cardiac support (MCS), International Society for Heart and Lung Transplantation grade ≥2R rejection, and mortality. Recipient risk scores were also investigated. Results: Leptin levels were significantly lower in patients with PGD than in those without PGD (median: 6.36 (IQR: 5.55–6.62) versus 7.54 (IQR = 6.71–10.44); p = 0.029). Higher ApoCII levels (median: 14.91 (IQR: 11.55–21.30) versus 10.31 (IQR = 10.02–13.07); p = 0.042) and ApoCIII levels (median: 60.32 (IQR: 43.00–81.66) versus 22.84 (IQR = 15.84–33.39); p = 0.005) were found in patients (n = 5) who died in the first 5 years after HTX. In patients who exhibited rejection (n = 4) in the first month after transplantation, the levels of adiponectin (median: 74.48 (IQR: 35.51–131.70) versus 29.96 (IQR: 19.86–42.28); p = 0.039), ApoCII (median: 20.11 (IQR: 13.06–23.54) versus 10.32 (IQR: 10.02–12.84); p = 0.007), and ApoCIII (median: 70.97 (IQR: 34.72–82.22) versus 26.33 (IQR: 17.18–40.17); p = 0.029) were higher than in the nonrejection group. Moreover, the pericardial thyroxine (T4) levels (median: 3.96 (IQR: 3.49–4.46) versus 4.69 (IQR: 4.23–5.77); p = 0.022) were lower in patients with rejection than in patients who did not develop rejection. Conclusion: Our results indicate that apolipoproteins can facilitate the monitoring of rejection and could be a useful tool in the forecasting of early and late complications. Full article

(This article belongs to the Special Issue Immune Regulations in Transplant)

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16 pages, 2770 KiB

Open AccessArticle

Downregulation of Swine Leukocyte Antigen Expression Decreases the Strength of Xenogeneic Immune Responses towards Renal Proximal Tubular Epithelial Cells

by Katharina Schmalkuche, Reinhard Schwinzer, Nadine Wenzel, Emilio Valdivia, Björn Petersen, Rainer Blasczyk and Constanca Figueiredo

Int. J. Mol. Sci. 2023, 24(16), 12711; https://doi.org/10.3390/ijms241612711 - 12 Aug 2023

Cited by 4 | Viewed by 1353

Abstract

Xenotransplantation reemerged as a promising alternative to conventional transplantation enlarging the available organ pool. However, success of xenotransplantation depends on the design and selection of specific genetic modifications and on the development of robust assays allowing for a precise assessment of tissue-specific immune responses. Nevertheless, cell-based assays are often compromised by low proliferative capacity of primary cells. Proximal tubular epithelial cells (PTECs) play a crucial role in kidney function. Here, we generated immortalized PTECs (imPTECs) by overexpression of simian virus 40 T large antigen. ImPTECs not only showed typical morphology and phenotype, but, in contrast to primary PTECs, they maintained steady cell cycling rates and functionality. Furthermore, swine leukocyte antigen (SLA) class I and class II transcript levels were reduced by up to 85% after transduction with lentiviral vectors encoding for short hairpin RNAs targeting β2-microglobulin and the class II transactivator. This contributed to reducing xenogeneic T-cell cytotoxicity (p < 0.01) and decreasing secretion of pro-inflammatory cytokines such as IL-6 and IFN-γ. This study showed the feasibility of generating highly proliferative PTECs and the development of tissue-specific immunomonitoring assays. Silencing SLA expression on PTECs was demonstrated to be an effective strategy to prevent xenogeneic cellular immune responses and may strongly support graft survival after xenotransplantation. Full article

(This article belongs to the Special Issue Immune Regulations in Transplant)

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20 pages, 7973 KiB

Open AccessArticle

TCR Sequencing in Mouse Models of Allorecognition Unveils the Features of Directly and Indirectly Activated Clonotypes

by Valeriy Tereshchenko, Daniil Shevyrev, Marina Fisher, Aleksei Bulygin, Julia Khantakova and Sergey Sennikov

Int. J. Mol. Sci. 2023, 24(15), 12075; https://doi.org/10.3390/ijms241512075 - 28 Jul 2023

Viewed by 1628

Abstract

Allorecognition is known to involve a large number of lymphocytes carrying diverse T-cell receptor repertoire. Thus, one way to understand allorecognition and rejection mechanisms is via high-throughput sequencing of T-cell receptors. In this study, in order to explore and systematize the properties of the alloreactive T-cell receptor repertoire, we modeled direct and indirect allorecognition pathways using material from inbred mice in vitro and in vivo. Decoding of the obtained T-cell receptor genes using high-throughput sequencing revealed some features of the alloreactive repertoires. Thus, alloreactive T-cell receptor repertoires were characterized by specific V-gene usage patterns, changes in CDR3 loop length, and some amino acid occurrence probabilities in the CDR3 loop. Particularly pronounced changes were observed for directly alloreactive clonotypes. We also revealed a clustering of directly and indirectly alloreactive clonotypes by their ability to bind a single antigen; amino acid patterns of the CDR3 loop of alloreactive clonotypes; and the presence in alloreactive repertoires of clonotypes also associated with infectious, autoimmune, and tumor diseases. The obtained results were determined by the modeling of the simplified allorecognition reaction in inbred mice in which stimulation was performed with a single MHCII molecule. We suppose that the decomposition of the diverse alloreactive TCR repertoire observed in humans with transplants into such simple reactions will help to find alloreactive repertoire features; e.g., a dominant clonotype or V-gene usage pattern, which may be targeted to correct the entire rejection reaction in patients. In this work, we propose several technical ways for such decomposition analysis, including separate modeling of the indirect alloreaction pathway and clustering of alloreactive clonotypes according to their ability to bind a single antigen, among others. Full article

(This article belongs to the Special Issue Immune Regulations in Transplant)

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13 pages, 1311 KiB

Open AccessArticle

Early Cytomegalovirus Reactivation in Renal Recipients Is Associated with High Levels of B Cell Maturation Antigen Transcript Expression Prior to Transplantation

by Rafael Alfaro, Luis Rodríguez-Aguilar, Santiago Llorente, Victor Jimenez-Coll, Helios Martínez-Banaclocha, José Antonio Galián, Carmen Botella, María Rosa Moya-Quiles, Manuel Muro-Perez, Alfredo Minguela, Isabel Legaz and Manuel Muro

Int. J. Mol. Sci. 2023, 24(13), 10491; https://doi.org/10.3390/ijms241310491 - 22 Jun 2023

Cited by 4 | Viewed by 1575

Abstract

Cytomegalovirus (CMV) infection is the most frequent infection episode in kidney transplant (KT) recipients. Reactivation usually occurs in the first three months after transplantation and is associated with higher cellular and/or antibody-mediated rejection rates and poorer graft performance. CMV induces the expression of BAFF (B-cell-activating factor, a cytokine involved in the homeostasis of B cells), which communicates signals for survival and growth to B cells and virus-specific plasma cells via the R-BAFF (BAFF receptor), TACI (the calcium modulator, the cyclophilin ligand interactor), and BCMA (B cell maturation antigen) receptors. These molecules of the BAFF system have also been suggested as biomarkers for the development of alloantibodies and graft dysfunction. This prospective study included 30 CMV-IgG seropositive KT recipients. The expression levels of the genes BAFF-R, transmembrane activator and CAML interactor (TACI), and B cell maturation antigen (BCMA) in peripheral blood leukocytes (PBL) pre-KT were determined using qPCR. qPCR was also used to monitor CMV reactivation in the first three months following KT. The remainder of the KT recipients were classified as CMV− reactivation, and those with more than 500 copies/mL in at least one sample were classified as CMV+ reactivation. There were no discernible variations in the BAFF-R and TACI transcript expression levels. In the CMV+ group, we examined the relationship between the transcript levels and peak viremia. Peak viremia levels and BCMA transcript levels showed a strong correlation. BAFF-R and TACI expressions showed no measurable differences. In patients with early CMV reactivation, high BCMA receptor expression was associated with increased plasmablast, lymphocyte B cell class-switched levels (LBCS), and viral load. Our findings demonstrate that pre-KT BCMA transcript levels increased in KT recipients with early CMV reactivation. These transcript levels positively correlate with peak viremia and weakly with plasmablast and LBCS levels in PBLs. Full article

(This article belongs to the Special Issue Immune Regulations in Transplant)

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