Review
Immunology
Ke Fan Bei, Sajad Moshkelgosha, Bo Jie Liu, Stephen Juvet
Summary: Replacement of diseased organs with healthy donor organs through transplantation is the best option for end-stage organ disease, but long-term survival is limited due to the use of immunosuppressants. Achieving allograft tolerance, where the graft function is maintained without the need for immunosuppression, has been the goal of transplant clinicians and scientists. Regulatory T cells (Tregs) have shown potential in preventing allograft rejection, but their role in intragraft functional diversification and spatial organization is still largely unknown.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Viswajit Mulpuru, Nidhi Mishra
Summary: The study aims to identify potential CTL epitopes in the SARS-CoV-2 Indian isolate for Indian population, analyze their immunogenicity and foreignness, and investigate their interactions with HLA system to confirm their candidacy as epitope candidates for vaccine development.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Jia-Nan Cheng, Wen Luo, Chengdu Sun, Zheng Jin, Xianghua Zeng, Peter B. Alexander, Zhihua Gong, Xin Xia, Xiaofang Ding, Shouxia Xu, Ping Zou, Yisong Y. Wan, Qingzhu Jia, Qi-Jing Li, Bo Zhu
Summary: Cancer immunotherapy efficacy can be improved by enhancing eosinophil infiltration through radiation, which also boosts the effectiveness of CD8(+) T cells and adoptive T cell therapy. Eosinophil mobilization may serve as a mechanistically relevant biomarker for predicting the effectiveness of pre-immunotherapy radiation and enhancing T cell-mediated immunotherapy against cancers.
Article
Health Care Sciences & Services
Longhao Sun, Yang Zhang, Tiantian Yang, Junhang Chen, Xuebin Zhang, Xiaoyu Liang
Summary: Regulatory T cell infiltration is associated with tumor development and prognosis in pancreatic ductal adenocarcinoma. This study reveals that insulin-like growth factor binding protein 2 (IGFBP2) is associated with regulatory T cell accumulation and promotes disease progression in PDAC by inducing immunosuppressive tumor microenvironment.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Immunology
Cecile Apert, Ariel O. Galindo-Albarran, Sarah Castan, Claire Detraves, Heloise Michaud, Nicola McJannett, Bart Haegeman, Simon Fillatreau, Bernard Malissen, Georg Hollander, Saulius Zuklys, Jeremy C. Santamaria, Olivier P. Joffre, Paola Romagnoli, Joost P. M. van Meerwijk
Summary: This study reevaluated the role of IL-2 and IL-15 in the development of regulatory T-lymphocytes (Treg) and found that IL-2 and IL-15 play important non-redundant quantitative and qualitative roles in intrathymic Treg development.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Medicine, General & Internal
Hoa Le Mai, Nicolas Degauque, Sabine Le Bot, Marie Rimbert, Karine Renaudin, Richard Danger, Florent Le Borgne, Clarisse Kerleau, Gaelle Tilly, Anais Vivet, Florent Delbos, Alexandre Walencik, Magali Giral, Sophie Brouard
Summary: The study found that the percentage and absolute number of CD28-CD8+ T cells were significantly increased in kidney transplant patients with antibody-mediated rejection (ABMR). Moreover, CD28-CD8+ T cells from patients with ABMR showed a more rigorous response to stimulation compared to their CD28+ counterparts. These findings suggest that differentiated CD28-CD8+ T cells, with increased frequency, number, and function, may play a role in the pathobiology of ABMR.
Article
Oncology
Satu Salmi, Anton Lin, Benjamin Hirschovits-Gerz, Mari Valkonen, Niina Aaltonen, Reijo Sironen, Hanna Siiskonen, Sanna Pasonen-Seppanen
Summary: In malignant cutaneous melanoma, FoxP3+ regulatory T cells and IDO play a role in creating an immunosuppressive tumor microenvironment. The expression of IDO in melanoma cells is associated with poor prognostic factors, and there is a positive correlation between the number of IDO+ tumor cells and FoxP3+ regulatory T cells.
Article
Cell Biology
Priyanka Chauhan, Shuxian Hu, Wen S. Sheng, James R. Lokensgard
Summary: Regulatory T-cells (Tregs) play critical roles in controlling cytotoxic T-cell responses against microglial cells and suppressing the production of tumor necrosis factor and interferon. Tregs can also reduce MHC-1 expression on microglial cells and decrease the production of interleukin-6.
Article
Immunology
Vasti Lozano-Ordaz, Yadira Rodriguez-Miguez, Angel E. Ortiz-Cabrera, Sujhey Hernandez-Bazan, Dulce Mata-Espinosa, Jorge Barrios-Payan, Rafael Saavedra, Rogelio Hernandez-Pando
Summary: This study compared the contribution of Treg cells, IDO, and HO-1 in mice infected with Mtb strains of different virulences. It found that these factors were detrimental for immune protection in mild virulence infection, but beneficial in highly virulent infection by regulating excessive inflammation.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Surgery
Suheyla Hasgur, Yosuke Yamamoto, Ran Fan, Michael Nicosia, Victoria Gorbacheva, Daniel Zwick, Motoo Araki, Robert L. Fairchild, Anna Valujskikh
Summary: Diminishing homeostatic proliferation of memory T cells is essential for improving the efficacy of lymphoablation in transplant recipients. The study identifies B cell Mincle as an important sensor for damage-associated molecular patterns released by the graft, demonstrating its role in clinically relevant settings of organ transplantation. Additionally, CD40 signaling induces T cell proliferation via a Mincle-dependent pathway.
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Article
Immunology
Alexandra Franziska Gulich, Ramona Rica, Caroline Tizian, Csilla Viczenczova, Kseniya Khamina, Thomas Faux, Daniela Hainberger, Thomas Penz, Remy Bosselut, Christoph Bock, Asta Laiho, Laura L. Elo, Andreas Bergthaler, Wilfried Ellmeier, Shinya Sakaguchi
Summary: The transcription factor MAZR partially compensates for the loss of Runx3 in CTLs, as demonstrated through transcriptome analysis. MAZR and Runx3 cooperatively regulate the expression of key genes in CTLs, while showing distinct functions in the differentiation of memory T cell subsets. This study provides insights into the complex interplay between MAZR and Runx3 in the development of CTL and memory T cell pools.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Dentistry, Oral Surgery & Medicine
Saki Nakane, Kentaro Imamura, Rio Hisanaga, Kazuyuki Ishihara, Atsushi Saito
Summary: The study demonstrated that CTLA-4-Ig can effectively inhibit bone resorption in periodontitis by affecting osteoclast differentiation and activity, potentially through the regulation of the NF-kappa B pathway and PP2A expression.
JOURNAL OF PERIODONTAL RESEARCH
(2021)
Article
Engineering, Biomedical
Yingying Shi, Yichao Lu, Chunqi Zhu, Zhenyu Luo, Xiang Li, Yu Liu, Mengshi Jiang, Xu Liu, Lihua Luo, Yongzhong Du, Jian You
Summary: Regulating lymphocytic ER unfolded protein response (UPR) could be a potential therapeutic breakthrough in alleviating graft rejection. These findings suggest that lymphocytic IRE1 alpha inactivation attenuates transplant rejection and prolongs graft survival, with limited effector function and memory commitment of host T-8. The combination of IRE1 alpha inhibition with immunosuppressant tacrolimus (FK506) shows an even higher immunosuppressive effect through synergistic regulation of inflammatory transcription factors.
Editorial Material
Immunology
Jens Geginat, Francesca Granucci
Summary: Regulatory T-cells (Tregs) are crucial for preventing autoimmunity and also play a role in immune stimulation. A recent study discovered that Tregs are a physiological source of IL-15, which is important for maintaining CD8(+) memory T-cells.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Article
Immunology
Aashli Pathni, Altug Ozcelikkale, Ivan Rey-Suarez, Lei Li, Scott Davis, Nate Rogers, Zhengguo Xiao, Arpita Upadhyaya
Summary: Cytotoxic T lymphocytes (CTLs) play a crucial role in killing infected cells. This study demonstrates that IL-12 can modulate the cytoskeleton and force exertion of CTLs, thereby enhancing their mechanical response to target cells.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Romy Steiner, Nina Pilat
Summary: Since the discovery of regulatory T cells (Tregs) as crucial regulators of immune tolerance, they have become a promising tool for inducing donor-specific tolerance in transplantation medicine. Various approaches, such as adoptive transfer, ex vivo expansion, and in vivo stimulation, have been explored to enhance Treg therapy. Furthermore, next generation concepts, such as CARs, TRUCKs, and BARs, are being investigated for improving Treg function. Clinical trials have shown promise, but long-term results and efficacy remain limited, and challenges for clinical translation remain open.
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Nina Pilat, Romy Steiner, Jonathan Sprent
Summary: The limited success of solid organ transplantation is influenced by the insufficiency of immunosuppressive regimens to control chronic rejection and late graft loss. However, regulatory T cells (Tregs) have shown potential in inducing allograft tolerance and prolonging graft survival. The first Treg-based clinical trials have yielded promising results, demonstrating the feasibility and safety of Treg therapy in organ transplantation. Nevertheless, there are still unresolved questions regarding Treg phenotype, dosage, antigen-specificity, adjunct immunosuppressants, and efficacy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Editorial Material
Urology & Nephrology
Nina Pilat
Summary: In this paper, the authors present a case study of hematopoietic chimerism and subsequent tolerance in a pediatric patient undergoing isolated kidney transplantation with syndromic combined immune deficiency. The findings not only emphasize the importance of the chimerism approach for tolerance induction in transplantation, but also provide the first evidence of hematopoietic stem cells in human kidneys. The commentary discusses the efficacy and risks of the chimerism approach for tolerance induction after solid organ transplantation, particularly in (pediatric) patients with immune deficiencies.
KIDNEY INTERNATIONAL
(2023)
Article
Multidisciplinary Sciences
Casie A. A. Pendexter, Omar Haque, Mohammadreza Mojoudi, Sarah Maggipinto, Marion Goutard, Simona Baicu, Alexandre G. G. Lellouch, James F. F. Markmann, Gerald Brandacher, Heidi Yeh, Shannon N. N. Tessier, Curtis Cetrulo, Korkut Uygun
Summary: Vascularized composite allografts (VCAs) are transplants of heterogenous tissue used to restore form and function after amputation or tissue loss. Rat limb VCA models have been used to study the pathophysiology of these transplants, but have mainly focused on hindlimb VCAs which do not anatomically translate to upper extremity transplantation. This study optimizes rat forelimb VCA procurement and sub-normothermic machine perfusion (SNMP) protocols, providing useful information for future upper extremity VCA preservation studies.
Article
Microbiology
Laura P. Kincer, Sarah Beth Joseph, Maria M. Gilleece, Blake M. Hauser, Sabrina Sizemore, Shuntai Zhou, Clara Di Germanio, Henrik Zetterberg, Dietmar Fuchs, Steven G. Deeks, Serena Spudich, Magnus Gisslen, Richard W. Price, Ronald Swanstrom
Summary: HIV-1 can persist in a latent reservoir in individuals receiving antiretroviral therapy, and rebound virus can be detected in the cerebrospinal fluid during treatment interruption. In this study, we found that high viral loads and clonally amplified viral lineages in the cerebrospinal fluid were correlated with the influx of white blood cells. Additionally, we did not observe rebound macrophage-tropic virus in the cerebrospinal fluid, indicating that the CNS may not be a source of this virus. We propose a model in which R5 T cell-tropic virus is released from infected T cells in the CNS during treatment interruption.
NATURE MICROBIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Julia Hofmann, Marlene Puehringer, Sabrina Steinkellner, Aline-Sophie Holl, Andras T. Meszaros, Stefan Schneeberger, Jakob Troppmair, Theresa Hautz
Summary: The implementation of ex vivo organ machine perfusion (MP) has increased the donor pool by enabling organ assessment and potential regeneration and treatment of marginal organs. While whole organ research is costly, in vitro models such as tissue slice cultures and organoids are more suitable for early stage research or studying specific disease mechanisms. This review discusses the role of oxidative stress during ex vivo MP and the suitability of different in vitro models for studying underlying mechanisms and testing treatment strategies.
Article
Biochemistry & Molecular Biology
Julia Hofmann, Andras T. Meszaros, Madita L. Buch, Florian Nardin, Verena Hackl, Carola J. Strolz, Bettina Zelger, Margot Fodor, Benno Cardini, Rupert Oberhuber, Thomas Resch, Annemarie Weissenbacher, Jakob Troppmair, Stefan Schneeberger, Theresa Hautz
Summary: The majority of liver transplantation organs come from brain-dead donors, but there is an increasing consideration for donation after circulatory death (DCD) organs to overcome the shortage. Normothermic machine perfusion (NMP) can restore metabolic activity and assess organ quality and function. In comparing DCD and brain-dead donors (DBD) livers during NMP, DCD livers initially showed greater impairment of mitochondrial function, but eventually recovered and performed similarly to DBD livers. Cytokine analysis showed elevated levels in DCD livers towards the end of NMP. This study suggests the potential for using more DCD organs for transplantation, but donor organ quality criteria should be developed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Jana K. Striefler, Phung T. Binder, Franziska Brandes, Daniel Rau, Silvan Wittenberg, David Kaul, Siyer Roohani, Armin Jarosch, Frederik M. Schaefer, Robert Oellinger, Sven Maerdian, Lars Bullinger, Kai -Uwe Eckardt, Jan Kruse, Anne Floercken
Summary: This study retrospectively analyzed sarcoma patients admitted to the ICU from 2005 to 2022. Sex, tumor localization, therapeutic intention, line of chemotherapy, SAPS II score, and SOFA score significantly impacted overall survival. The study confirms the predictive relevance of established sepsis and performance scores in sarcoma patients.
CANCER MANAGEMENT AND RESEARCH
(2023)
Article
Medicine, General & Internal
Ruben Bellotti, Benno Cardini, Carola J. Strolz, Stefan Staettner, Rupert Oberhuber, Eva Braunwarth, Thomas Resch, Stefan Scheidl, Christian Margreiter, Stefan Schneeberger, Dietmar Ofner, Manuel Maglione
Summary: This study compared three different reconstruction techniques for pancreaticoduodenectomy, and found that they did not significantly affect the rates of postoperative complications. However, pancreatogastrostomy had a higher incidence of post-pancreatectomy hemorrhage, indicating the need for meticulous hemostasis during the surgery.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Immunology
Arvid Eden, Frida Rydberg, Aylin Yilmaz, Lars Hagberg, Johanna Gostner, Staffan Nilsson, Dietmar Fuchs, Magnus Gisslen
Summary: For people with HIV initiating ART during chronic infection, the occurrence of residual CNS immune activation is not correlated with pretreatment immune status, even when treatment is initiated at high CD4(+) T-cell counts, suggesting that the CNS reservoir is not differentially affected by the timing of ART initiation during chronic infection.
OPEN FORUM INFECTIOUS DISEASES
(2023)
Article
Biochemistry & Molecular Biology
Katharina Obermoser, Natascha Brigo, Andrea Schroll, Pablo Monfort-Lanzas, Johanna M. Gostner, Sabine Engl, Simon Geisler, Miriam Knoll, Harald Schennach, Guenter Weiss, Dietmar Fuchs, Rosa Bellmann-Weiler, Katharina Kurz
Summary: This pilot study investigated the effects of a multi-strain probiotic preparation on fatigue, depression, and quality of life in patients with post-infectious fatigue. The results showed that both the probiotic and placebo groups experienced improvements, but the probiotic group had greater improvements. After 6 months, the probiotic group had significantly lower fatigue and depression scores, as well as improved quality of life.
Article
Biotechnology & Applied Microbiology
John R. Aggas, Sara Abasi, Carolyn Ton, Sara Salehi, Renee Liu, Gerald Brandacher, Warren L. Grayson, Anthony Guiseppi-Elie
Summary: Vascularized composite allotransplantation is widely used for injuries to complex anatomical structures. Prolonged cold storage damages grafts and limits their viability. Tissue ischemia is a major concern and can lead to poor transplantation outcomes. This perspective introduces MMBIS as a noninvasive monitoring technique to assess graft preservation efficacy and viability in real-time. Developing MMBIS and incorporating AI can improve transplantation outcomes by stratifying allografts.
BIOENGINEERING-BASEL
(2023)
Review
Medicine, Research & Experimental
Carolyn Ton, Sara Salehi, Sara Abasi, John R. Aggas, Renee Liu, Gerald Brandacher, Anthony Guiseppi-Elie, Warren L. Grayson
Summary: Vascularized composite allotransplantation plays a crucial role in improving quality of life and restoring functionality. However, the complex tissue composition of VCAs presents unique clinical challenges, increasing the risk of transplant rejection. The development of methods to evaluate VCAs is crucial for mitigating rejection.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Gastroenterology & Hepatology
Katharina Esswein, Marco Volpi, Marijana Ninkovic, Veronika Kroepfl, Elisabeth Gasser, Andreas Lorenz, Lea Stecher, Reinhold Kafka-Ritsch, Stefan Schneeberger, Dietmar Oefner, Alexander Perathoner
Summary: This study aimed to analyze the adherence to intensive follow-up and the risk of recurrence in patients with colon cancer in UICC stages I and II. The results showed that the risk of recurrence was low in early tumor stages, suggesting that a less intensive follow-up protocol is reasonable for these patients.
INTERNATIONAL JOURNAL OF COLORECTAL DISEASE
(2023)
Article
Oncology
Felix J. Krendl, Franka Messner, Gregor Laimer, Angela Djanani, Andreas Seeber, Georg Oberhuber, Dietmar Oefner, Dominik Wolf, Stefan Schneeberger, Reto Bale, Christian Margreiter
Summary: This study presents the experience in managing liver metastases from intracranial SFTs/HPCs. The results suggest that a multimodal treatment concept, including surgery, loco-regional and systemic therapies, can achieve long-term survival.
