Current immunosuppressants have nonspecific immuosuppressive effects, and are not helpful for tolerance induction. Consequently, transplant patients cannot discontinue using them, and their nonspecific immunosuppressive effects result in many side effects, including infection and malignancy. However, most of cellular immunotherapy can have donor antigen-specific immunsuppressive effects. Therefore, cell therapy could be an alternative or adjunctive to nonspecific immunosuppressants. Polyclonal or antigen-specific Foxp3+ regulatory T cells have been actively tried for prevention of acute rejection, treatment of chronic rejection, or tolerance induction in clinical trials. Regulatory macrophages are also under clinical trials for kidney transplant patients. IL-10-secreting type 1 regulatory T cells and donor- or recipient-derived tolerogenic dendritic cells will also be used for immunoregulation in clinical trials of kidney transplantation. These cells have antigen-specific immunoregulatory effects. Mesenchymal stromal cells (MSCs) have good proliferative capacity and immunosuppressive actions independently of major histocompatibility complex; therefore, even third-party MSCs can be stored and used for many patients. Cell therapy using various immunoregulatory cells is now promising for not only reducing side effects of nonspecific immunosuppressants but also induction of immune tolerance, and is expected to contribute to better outcomes in transplant patients.
Cell- and Tissue-Based Therapy* ; Dendritic Cells ; Humans ; Immune Tolerance ; Immunosuppressive Agents ; Immunotherapy ; Kidney ; Kidney Transplantation* ; Macrophages ; Major Histocompatibility Complex ; Mesenchymal Stromal Cells ; T-Lymphocytes, Regulatory ; Tissue Donors

Long-term survivors in renal transplantation have been increasing, as medical care has improved in addition to development of new immunosuppressants. Therefore, cardiovascular disease, especially ischemic heart disease and chronic allograft dysfunction have become main obstacles to longer survival and better quality of life. Dyslipidemia, which is a well-known risk factor of ischemic heart disease in general population, is more common in renal transplantation patients. Moreover, dyslipidemia is suggested as a nonimmunological risk factor of chronic allograft dysfunction. Therefore, it is important to manage dyslipidemia properly to improve patient and graft survival in renal transplantation. But, specific approach, tailored to renal transplant patients is necessary in the treatment of dyslipidemia, because there are significant differences between renal transplantation patients and general population. We present here, epidemiology, mechanism, and impact of dyslipidemia on ischemic heart disease and chronic allograft dysfunction, and overall approach to dyslipidemia in renal transplantation patients, including treatment guideline.
Allografts ; Cardiovascular Diseases ; Dyslipidemias* ; Epidemiology ; Graft Survival ; Humans ; Immunosuppressive Agents ; Kidney Transplantation ; Myocardial Ischemia ; Quality of Life ; Risk Factors ; Survivors

Foreign antigen recognition is the ability of immune cells to distinguish self from nonself, which is crucial for immune responses in both invertebrates and vertebrates. In vertebrates, T cells play a pivotal role in graft rejection by recognizing alloantigens presented by antigen-presenting cells through direct, indirect, or semidirect pathways.B cells also significantly contribute to the indirect presentation of antigens to T cells.Innate immune cells, such as dendritic cells, identify pathogen- or danger-associated molecular patterns through pattern recognition receptors, thereby facilitating effective antigen presentation to T cells. Recent studies have shown that innate immune cells, including macrophages and NK cells, can recognize allogeneic or xenogeneic antigens using immune receptors like CD47 or activating NK receptors, instead of pattern recognition receptors. Additionally, macrophages and NK cells are capable of exhibiting memory responses to alloantigens, although these responses are shorter than those of adaptive memory. T cells also recognize xenoantigens through either direct or indirect presentation. Notably, macrophages and NK cells can directly recognize xenoantigens via surface immune receptors in an antibody-independent manner, or they can be activated in an antibody-dependent manner. Advances in our understanding of the recognition mechanisms of adaptive and innate immunity against allogeneic and xenogeneic antigens may improve our understanding of graft rejection.

Foreign antigen recognition is the ability of immune cells to distinguish self from nonself, which is crucial for immune responses in both invertebrates and vertebrates. In vertebrates, T cells play a pivotal role in graft rejection by recognizing alloantigens presented by antigen-presenting cells through direct, indirect, or semidirect pathways.B cells also significantly contribute to the indirect presentation of antigens to T cells.Innate immune cells, such as dendritic cells, identify pathogen- or danger-associated molecular patterns through pattern recognition receptors, thereby facilitating effective antigen presentation to T cells. Recent studies have shown that innate immune cells, including macrophages and NK cells, can recognize allogeneic or xenogeneic antigens using immune receptors like CD47 or activating NK receptors, instead of pattern recognition receptors. Additionally, macrophages and NK cells are capable of exhibiting memory responses to alloantigens, although these responses are shorter than those of adaptive memory. T cells also recognize xenoantigens through either direct or indirect presentation. Notably, macrophages and NK cells can directly recognize xenoantigens via surface immune receptors in an antibody-independent manner, or they can be activated in an antibody-dependent manner. Advances in our understanding of the recognition mechanisms of adaptive and innate immunity against allogeneic and xenogeneic antigens may improve our understanding of graft rejection.

Foreign antigen recognition is the ability of immune cells to distinguish self from nonself, which is crucial for immune responses in both invertebrates and vertebrates. In vertebrates, T cells play a pivotal role in graft rejection by recognizing alloantigens presented by antigen-presenting cells through direct, indirect, or semidirect pathways.B cells also significantly contribute to the indirect presentation of antigens to T cells.Innate immune cells, such as dendritic cells, identify pathogen- or danger-associated molecular patterns through pattern recognition receptors, thereby facilitating effective antigen presentation to T cells. Recent studies have shown that innate immune cells, including macrophages and NK cells, can recognize allogeneic or xenogeneic antigens using immune receptors like CD47 or activating NK receptors, instead of pattern recognition receptors. Additionally, macrophages and NK cells are capable of exhibiting memory responses to alloantigens, although these responses are shorter than those of adaptive memory. T cells also recognize xenoantigens through either direct or indirect presentation. Notably, macrophages and NK cells can directly recognize xenoantigens via surface immune receptors in an antibody-independent manner, or they can be activated in an antibody-dependent manner. Advances in our understanding of the recognition mechanisms of adaptive and innate immunity against allogeneic and xenogeneic antigens may improve our understanding of graft rejection.

Foreign antigen recognition is the ability of immune cells to distinguish self from nonself, which is crucial for immune responses in both invertebrates and vertebrates. In vertebrates, T cells play a pivotal role in graft rejection by recognizing alloantigens presented by antigen-presenting cells through direct, indirect, or semidirect pathways.B cells also significantly contribute to the indirect presentation of antigens to T cells.Innate immune cells, such as dendritic cells, identify pathogen- or danger-associated molecular patterns through pattern recognition receptors, thereby facilitating effective antigen presentation to T cells. Recent studies have shown that innate immune cells, including macrophages and NK cells, can recognize allogeneic or xenogeneic antigens using immune receptors like CD47 or activating NK receptors, instead of pattern recognition receptors. Additionally, macrophages and NK cells are capable of exhibiting memory responses to alloantigens, although these responses are shorter than those of adaptive memory. T cells also recognize xenoantigens through either direct or indirect presentation. Notably, macrophages and NK cells can directly recognize xenoantigens via surface immune receptors in an antibody-independent manner, or they can be activated in an antibody-dependent manner. Advances in our understanding of the recognition mechanisms of adaptive and innate immunity against allogeneic and xenogeneic antigens may improve our understanding of graft rejection.

Regulatory T cells (Treg) naturally rein in immune attacks, and they can inhibit rejection of transplanted organs and even reverse the progression of autoimmune diseases in mice. The initial safety trials of Treg against graft-versus-host disease (GVHD) provided evidence that the adoptive transfer of Treg is safe and capable of limiting disease progression. Supported by such evidence, numerous clinical trials have been actively investigating the efficacy of Treg targeting autoimmune diseases, type I diabetes, and organ transplant rejection, including kidney and liver. The limited quantity of Treg cells harvested from peripheral blood and subsequent in vitro culture have posed a great challenge to large-scale clinical application of Treg; nevertheless, the concept of CAR (chimeric antigen receptor)-Treg has emerged as a potential resolution to the problem. Recently, two CAR-T therapies, tisagenlecleucel and axicabtagene ciloleucel, were approved by the US FDA for the treatment of refractory or recurrent acute lymhoblastic leukemia. This approval could serve as a guideline for the production protocols for other genetically engineered T cells for clinical use as well. The phase I and II clinical trials of these agents has demonstrated that genetically engineered and antigen-targeting T cells are safe and efficacious in humans. In conclusion, both the promising results of Treg cell therapy from the clinical studies and the recent FDA approval of CAR-T therapies are paving the way for CAR-Treg therapy in clinical use.
Adoptive Transfer ; Animals ; Autoimmune Diseases ; Cell- and Tissue-Based Therapy* ; Disease Progression ; Graft vs Host Disease ; Humans ; In Vitro Techniques ; Kidney ; Leukemia ; Liver ; Mice ; T-Lymphocytes ; T-Lymphocytes, Regulatory* ; Transplantation ; Transplants

Macrophage accumulation has been recognized as a feature of allograft rejection, however, the role of macrophages in rejection remains underappreciated. Macrophages are present within graft tissues throughout the lifespan of the graft, including acute rejection episodes. Recent advances in macrophage biology have demonstrated that different types of macrophages in grafts serve a range of functions, including promotion or attenuation of inflammation, participation in innate and adaptive immune responses, and mediation of tissue injury, fibrosis, and tissue repair. Macrophages contribute to both the innate and acquired arms of the alloimmune response, and, thus, may be involved in all aspects of acute and chronic allograft rejection. Macrophages are also involved in hyperacute and acute vascular rejection of xenografts. A deeper understanding of how macrophages accumulate within grafts and of the factors that control differentiation and function of these cells could lead to identification of novel therapeutic targets in transplantation.
Arm ; Biology ; Fibrosis ; Graft Rejection ; Inflammation ; Macrophages ; Negotiating ; Rejection (Psychology) ; Transplantation, Heterologous ; Transplantation, Homologous ; Transplants

No abstract available.
Kidney ; Kidney Transplantation

BACKGROUND: Hepatitis B virus (HBV)-associated glomerulonephritis (HBGN) occurs with high prevalence in Asia, and accounts for over 30% of secondary glomerulonephritis in Korea. However, the association between HLA and HBGN has been hardly reported upon in the literature. METHODS: A total of 50 Korean patients with HBGN, 100 HBsAg (-) healthy controls and 89 HBsAg (+) controls (subjects with chronic HBV infection, HBsAg positive at least for 6 months) were included. HLA-DR typing was done using a reverse sequence specific oligonucleotide typing kit and HLA-DRB1 genotyping was done for HLA-DR2 positive samples by PCR-single strand conformational polymorphism method. RESULTS: In the HBGN patients, HLA-DR2 was highly significantly increased compared with HBsAg (-) controls (p=0.0002, corrected p=0.002, OR=4.0) and also compared with HBsAg (+) controls (p= 0.0005, corrected p=0.006, OR=3.7). Different HLA- DR2 alleles were strongly associated with different pathologic subtypes of HBGN: DRB1*1502 was associated with membranoproliferative glomerulonephritis (MPGN) (p=0.0003, corrected p=0.004, OR=14.5), and DRB1*1501 with membranous nephropathy (MN) (p= 0.05, OR=3.8). These associations were also found to be significant compared with HBsAg (+) controls (HBV-MPGN, p=0.002; HBV-MN, p=0.04). DR13 was found to have some protective effect in HBV infection (p=0.01, OR=0.3) and DR11 was found to be weakly associated with HBV infection (p=0.01, OR= 4.6), however these HLA alleles were not associated with disease susceptibility to HBGN. CONCLUSION: These results suggest that HLA- DR2 or a closely associated genetic factor is associated with disease susceptibility to HBGN, and different HLA-DR2 subtypes are associated with different pathologic subtypes of HBGN in Koreans.
Alleles ; Asia ; Disease Susceptibility ; Fibrinogen ; Glomerulonephritis* ; Glomerulonephritis, Membranoproliferative ; Glomerulonephritis, Membranous ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Hepatitis B* ; Hepatitis* ; HLA-DR Antigens* ; HLA-DR2 Antigen ; HLA-DRB1 Chains ; Humans ; Korea ; Prevalence