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immunopathogenesis transplant

Hidemi Suzuki, Atsushi Hata, Yuki Shina, Takamasa Yun, Kazuhisa Tanaka, Yuichi Sakairi, Hironobu Wada, Taiki Fujiwara, Takahiro Nakajima, Takekazu Iwata, Masako Chiyo, Shigetoshi Yoshida, Ichiro Yoshino
Chronic lung allograft dysfunction (CLAD) is a critical impediment to the long-term survival after lung transplantation. A rat orthotopic lung transplantation model was developed in the early 1970s, and using this model, our laboratory has shown that the immunopathogenesis of CLAD involves both allogeneic immunity and autoimmunity. However, further investigation of CLAD is limited by the scarcity of transgenic and knockout strains. The model most widely used to study CLAD, the mouse model of heterotopic tracheal transplantation, has some incomplete pathophysiologic features of CLAD, which limits the utility of this model...
October 2016: Kyobu Geka. the Japanese Journal of Thoracic Surgery
William Hoffman, Fadi G Lakkis, Geetha Chalasani
B cells play a central role in the immunopathogenesis of glomerulonephritides and transplant rejection. B cells secrete antibodies that contribute to tissue injury via multiple mechanisms. In addition, B cells contribute to disease pathogenesis in autoimmunity and alloimmunity by presenting antigens as well as providing costimulation and cytokines to T cells. B cells also play an immunomodulatory role in regulating the immune response by secreting cytokines that inhibit disease onset and/or progression. B cell-targeted approaches for treating immune diseases of the kidney and other organs have gained significant momentum...
January 7, 2016: Clinical Journal of the American Society of Nephrology: CJASN
Shivesh Punit, Philip E Dubé, Cambrian Y Liu, Nandini Girish, M Kay Washington, D Brent Polk
BACKGROUND & AIMS: Tumor necrosis factor receptor 2 (TNFR2, Tnfrsf1b) regulates multiple aspects of immune function, but little is known about its role in the immunopathogenesis of inflammatory bowel disease (IBD). We investigated whether TNFR2 restricts the activity of specific immune cell subtypes to protect against the development of colitis in mice. METHODS: Tnfr2(-/-) mice were crossed with interleukin (Il) 10(-/-) mice, which spontaneously develop colitis, to generate Il10(-/-)Tnfr2(-/-) mice...
October 2015: Gastroenterology
Farhad Sahebjam, John M Vierling
Autoimmune hepatitis is a chronic liver disease putatively caused by loss of tolerance to hepatocyte-specific autoantigens. It is characterized by female predilection, elevated aminotransferase levels, autoantibodies, increased γ-globulin or IgG levels and biopsy evidence of interface hepatitis. It is currently divided into types 1 and 2, based on expression of autoantibodies. Autoantigenic epitopes have been identified only for the less frequent type 2. Although autoimmune hepatitis occurs in childhood, this review focuses on disease in adults...
June 2015: Frontiers of Medicine
Elizabeth A Lendermon, Jeffrey M Dodd-o, Tiffany A Coon, Hannah L Miller, Sudipto Ganguly, Iulia Popescu, Christopher P O'Donnell, Nayra Cardenes, Melanie Levine, Mauricio Rojas, Nathaniel M Weathington, Jing Zhao, Yutong Zhao, John F McDyer
Acute cellular rejection is a known risk factor for the development of obliterative bronchiolitis, which limits the long-term survival of lung transplant recipients. However, the T cell effector mechanisms in both of these processes remain incompletely understood. Using the mouse orthotopic lung transplant model, we investigated whether C57BL/6 T-bet(-/-) recipients of major histocompatibility complex (MHC)-mismatched BALB/c lung grafts develop rejection pathology and allospecific cytokine responses that differ from wild-type mice...
May 2015: American Journal of Respiratory Cell and Molecular Biology
Yureeda Qazi, Pedram Hamrah
Corneal transplantation is among the most successful solid organ transplants. However, despite low rejection rates of grafts in the 'low-risk' setting, rejection can be as high as 70% when grafted into 'high-risk' recipient beds. Under normal homeostatic conditions, the avascular cornea provides a unique environment that facilitates immune and angiogenic privilege. An imbalance in pro-inflammatory, angiogenic and lymphangiogenic mediators leads to a breakdown in corneal immune privilege with a consequent host response against the donor graft...
November 20, 2013: Journal of Clinical & Cellular Immunology
Joo Youn Oh, Hyun Ju Lee, Ah Young Ko, Jung Hwa Ko, Mee Kum Kim, Won Ryang Wee
PURPOSE: We investigated the phenotype of macrophages infiltrating rejected corneal allografts. METHODS: We performed allogeneic or syngeneic corneal transplantation in mice, and humanely killed animals at day 28 during allograft rejection when 60% of corneal allografts were rejected. We divided allografts into two groups: grafts with rejection as rejectors and grafts without rejection as nonrejectors, and analyzed for macrophage infiltration and their phenotype using immunohistochemistry...
2013: Investigative Ophthalmology & Visual Science
Nataraju Angaswamy, Venkataswarup Tiriveedhi, Nayan J Sarma, Vijay Subramanian, Christina Klein, Jason Wellen, Surendra Shenoy, William C Chapman, T Mohanakumar
Recent studies strongly suggest an increasing role for immune responses against self-antigens (Ags) which are not encoded by the major histocompatibility complex in the immunopathogenesis of allograft rejection. Although, improved surgical techniques coupled with improved methods to detect and avoid sensitization against donor human leukocyte antigen (HLA) have improved the immediate and short term function of transplanted organs. However, acute and chronic rejection still remains a vexing problem for the long term function of the transplanted organ...
November 2013: Human Immunology
Chun Yuen J Chung, Dirk Ysebaert, Zwi N Berneman, Nathalie Cools
In general, immunological tolerance is acquired upon treatment with non-specific immunosuppressive drugs. This indiscriminate immunosuppression of the patient often causes serious side-effects, such as opportunistic infectious diseases. Therefore, the need for antigen-specific modulation of pathogenic immune responses is of crucial importance in the treatment of inflammatory diseases. In this perspective, dendritic cells (DCs) can have an important immune-regulatory function, besides their notorious antigen-presenting capacity...
2013: Clinical & Developmental Immunology
Chin-Nien Lee, Andrew M Lew, Li Wu
Type 1 diabetes (T1D) is the result of T-cell mediated autoimmune destruction of pancreatic islet β-cells. The two current treatments for T1D are based on insulin or islet-cell replacement rather than the pathogenesis of T1D and remain problematic. Islet/pancreas transplantation does not cater for the majority of sufferers due to the lack of supply of organs and the need for continuous immunosuppression regimens. The mainstay treatment is insulin replacement, but this is disruptive to lifestyle and does not protect against severe long-term complications...
June 2013: Immunotherapy
Amar Safdar
Response to systemic antifungal therapy alone remains disproportionately less satisfactory in immunosuppressed transplant and oncology patients. As insight in fungal immunopathogenesis forges ahead, interventions for boosting immune functions along with antimicrobial drugs has shown promise in preclinical experiments. The clinical experience with immunotherapy for invasive mold disease is limited. Most studies have involved small numbers of patients at a single institution or data collected retrospectively...
July 2013: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Haseeb Ilias Basha, Sabarinathan Ramachandran, Venkataswarup Tiriveedhi, Masashi Takenaka, Vijay Subramanian, Dilip S Nath, Nicholas Benshoff, G Alec Patterson, Thalachallour Mohanakumar
BACKGROUND: The IL-17 axis is implicated in pathogenesis of chronic rejection after human lung transplantation. Using a murine model of obliterative airway disease (OAD), we recently demonstrated that Abs to MHC class I antigens can induce immune responses to self-antigens that contributes to immunopathogenesis of chronic rejection. Using a murine model of OAD, we determined the role of IL-17 family members in induction of autoimmunity leading to OAD after ligation of MHC class I. METHODS: Anti-MHC class I or control antibodies (Abs) were administered intrabronchially to wild-type (WT) and IL-17a knock out (IL-17A-/-) C57BL/6...
January 27, 2013: Transplantation
Thomas Lehrnbecher, Markus Kalkum, Jackson Champer, Lars Tramsen, Stanislaw Schmidt, Thomas Klingebiel
Despite the availability of new antifungal compounds, morbidity and mortality of invasive aspergillosis are still unacceptably high, in particular in immunocompromised patients such as patients with hematological malignancies or allogeneic hematopoietic stem cell or solid organ transplant recipients. Over the last decades, our knowledge of the immunopathogenesis of invasive aspergillosis has greatly advanced. This, in turn, provided critical information to augment host immunity against fungal pathogens. Potential approaches for enhancing the host immune system in the combat against Aspergillus include the administration of effector and regulatory cells (e...
2013: Current Pharmaceutical Design
Ramesh Akkina
Work with human specific viruses will greatly benefit from the use of an in vivo system that provides human target cells and tissues in a physiological setting. In this regard humanized mice (hu-Mice) have played an important role in our understanding of viral pathogenesis and testing of therapeutic strategies. Limitations with earlier versions of hu-Mice that lacked a functioning human immune system are currently being overcome. The new generation hu-Mouse models are capable of multilineage human hematopoiesis and generate T cells, B cells, macrophages and dendritic cells required for an adaptive human immune response...
January 5, 2013: Virology
Vijay Subramanian, Thalachallour Mohanakumar
Despite progress in the field of organ transplantation for improvement in graft survival and function, long-term graft function is still limited by the development of chronic allograft rejection. Various immune-mediated and nonimmune-mediated processes have been postulated in the pathogenesis of chronic rejection. In this review, the authors discuss the important role of alloimmune responses to donor-specific antigens and autoimmune responses to tissue restricted self-antigens in the immunopathogenesis of chronic rejection following solid organ transplantation...
September 2012: Expert Review of Clinical Immunology
Moses T Bility, Liguo Zhang, Michael L Washburn, T Anthony Curtis, Grigoriy I Kovalev, Lishan Su
Establishing a small animal model that accurately recapitulates hepatotropic pathogens, including hepatitis C virus (HCV) infection and immunopathogenesis, is essential for the study of hepatitis virus-induced liver disease and for therapeutics development. This protocol describes our recently developed humanized mouse model for studying HCV and other hepatotropic infections, human immune response and hepatitis and liver fibrosis. The first 5-h stage is the isolation of human liver progenitor and hematopoietic stem cells from fetal liver...
September 2012: Nature Protocols
Hidemi Suzuki, Lin Fan, David S Wilkes
Orthotopic lung transplantation in rats was first reported by Asimacopoulos and colleagues in 1971 (1). Currently, this method is well accepted and standardized not only for the study of allo-rejection but also between syngeneic strains for examining mechanisms of ischemia-reperfusion injury after lung transplantation. Although the application of the rat and other large animal model (2) contributed significantly to the elucidation of these studies, the scope of those investigations is limited by the scarcity of knockout and transgenic rats...
2012: Journal of Visualized Experiments: JoVE
Nayan J Sarma, Venkataswarup Tiriveedhi, Nataraju Angaswamy, T Mohanakumar
Significant progress has been made in preventing acute allograft rejection following solid organ transplantation resulting in improved allograft survival. However, long term function still remains disappointing primarily due to chronic allograft rejection. Alloimmune responses primarily defined by the development of antibodies (Abs) to donor mismatched major histocompatibility antigens during the post-transplantation period have been strongly correlated to the development of chronic rejection. In addition, recent studies have demonstrated an important role for autoimmunity including the development of Abs to organ specific self-antigens in the pathogenesis of chronic allograft rejection...
December 2012: Human Immunology
Smita Gupta
Type 1 diabetes is an autoimmune disease that gradually destructs insulin-producing beta cells. Over the years, clinicians' knowledge regarding the immunopathogenesis of this disease has greatly increased. Immunotherapies that can change the course of immune-mediated destruction and preserve and possibly regenerate the pancreatic beta cells seem to be promising in preclinical trials but so far have been unsuccessful in human studies. This article reviews the important immune interventions for type 1 diabetes that have been tried so far targeting the different stages of disease development and provides an insight into what the future might hold...
May 2012: Medical Clinics of North America
Francisco Salcido-Ochoa, Nurhashikin Yusof, Susan Swee-Shan Hue, Doreen Haase, Terence Kee, Olaf Rotzschke
The existence of T-cell subsets naturally committed to perform immunoregulation has led to enthusiastic efforts to investigate their role in the immunopathogenesis of transplantation. Being able to modulate alloresponses, regulatory T cells could be used as an immunodiagnostic tool in clinical kidney transplantation. Thus, the measurement of Foxp3 transcripts, the presence of regulatory T cells in kidney biopsies, and the phenotypic characterisation of the T-cell infiltrate could aid in the diagnosis of rejection and the immune monitoring and prediction of outcomes in kidney transplantation...
2012: Journal of Transplantation
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