-
Frontiers in Immunology 2021
Topics: Animals; Desensitization, Immunologic; Disease Models, Animal; Graft Rejection; HLA Antigens; Humans; Isoantigens; Organ Transplantation; Transplantation, Homologous
PubMed: 34721444
DOI: 10.3389/fimmu.2021.784472 -
Frontiers in Immunology 2020Over the past few decades, we have witnessed a decline in the rates of acute rejection without significant improvement in chronic rejection. Current treatment strategies... (Review)
Review
Over the past few decades, we have witnessed a decline in the rates of acute rejection without significant improvement in chronic rejection. Current treatment strategies principally target the adaptive immune response and not the innate response. Therefore, better understanding of innate immunity in transplantation and how to target it is highly desirable. Here, we review the latest advances in innate immunity in transplantation focusing on the roles and mechanisms of innate allorecognition and memory in myeloid cells. These novel concepts could explain why alloimmune response do not abate over time and shed light on new molecular pathways that can be interrupted to prevent or treat chronic rejection.
Topics: Animals; Graft Rejection; Graft Survival; Histocompatibility Antigens Class I; Humans; Immunity, Innate; Immunologic Memory; Immunosuppressive Agents; Isoantigens; Organ Transplantation; Transplantation Tolerance; Treatment Outcome
PubMed: 32547540
DOI: 10.3389/fimmu.2020.00918 -
The Journal of Experimental Medicine May 2022Pregnancy is recognized as a spontaneously acquired state of immunological tolerance by the mother to her semi-allogeneic fetus, but it is a major cause of... (Review)
Review
Pregnancy is recognized as a spontaneously acquired state of immunological tolerance by the mother to her semi-allogeneic fetus, but it is a major cause of allosensitization in candidates for organ transplantation. This sensitization, assessed by the presence of anti-HLA IgG, contributes to sex disparity in access to transplantation and increases the risk for rejection and graft loss. Understanding this dual tolerance/sensitization conundrum may lead to new strategies for equalizing access to transplantation among sexes and improving transplant outcomes in parous women. Here, we review the clinical evidence that pregnancy results in humoral sensitization and query whether T cell responses are sensitized. Furthermore, we summarize preclinical evidence on the effects of pregnancy on fetus-specific CD4+ conventional, regulatory, and CD8+ T cells, and humoral responses. We end with a discussion on the impact of the divergent effects that pregnancy has upon alloantigen re-encounter in the context of solid organ transplantation, and how these insights point to a therapeutic roadmap for controlling pregnancy-dependent allosensitization.
Topics: Female; Graft Rejection; HLA Antigens; Hematopoietic Stem Cell Transplantation; Humans; Immune Tolerance; Isoantigens; Organ Transplantation; Pregnancy
PubMed: 35416935
DOI: 10.1084/jem.20211493 -
Frontiers in Immunology 2021Memory B cells play an important role in immunity to pathogens as these cells are poised to rapidly differentiate into antibody-secreting cells upon antigen... (Review)
Review
Memory B cells play an important role in immunity to pathogens as these cells are poised to rapidly differentiate into antibody-secreting cells upon antigen re-encounter. Memory B cells also develop over the course of HLA-sensitization during pregnancy and transplantation. In this review, we discuss the potential contribution of memory B cells to pregnancy sensitization as well as the impact of these cells on transplant candidacy and outcomes. We start by summarizing how B cell subsets are altered in pregnancy and discuss what is known about HLA-specific B cell responses given our current understanding of fetal antigen availability in maternal secondary lymphoid tissues. We then review the molecular mechanisms governing the generation and maintenance of memory B cells during infection - including the role of T follicular helper cells - and discuss the experimental evidence for the development of these cells during pregnancy. Finally, we discuss how memory B cells impact access to transplantation and transplant outcomes for a range of transplant recipients.
Topics: Animals; Antibodies; B-Lymphocytes; Female; Fetus; HLA Antigens; Humans; Immunologic Memory; Isoantigens; Pregnancy
PubMed: 34276679
DOI: 10.3389/fimmu.2021.688987 -
Poultry Science Feb 2016Alloantigen systems are a broad group of molecules found on various cell types, including erythrocytes and lymphocytes. These alloantigens, identified via specific... (Review)
Review
Alloantigen systems are a broad group of molecules found on various cell types, including erythrocytes and lymphocytes. These alloantigens, identified via specific polyclonal or monoclonal antibodies or molecular methods, have demonstrated effects on immune responses. Erythrocyte alloantigens include the A, B, C, D, E, H, I, J, K, L, N, P, and R systems. Highly polymorphic alloantigen B has been identified as the chicken major histocompatibility complex (MHC). The other twelve systems have a variable degree of polymorphism as well as impact on immune measurements or responses against pathogens. Selection for immune characters altered allele frequencies for particular alloantigen systems. Three lymphocyte alloantigens, Bu-1, Ly-4 and Th-1 have more limited polymorphism but still influence responses against viral pathogens, Rous sarcoma virus and Marek's disease. Together, these erythrocyte and lymphocyte systems contribute to the overall immunity. Identification of the specific alloantigen proteins remains crucial to understanding their immune contribution.
Topics: Animals; Avian Proteins; Chickens; Erythrocytes; Immunity, Innate; Isoantigens; Lymphocytes
PubMed: 26527702
DOI: 10.3382/ps/pev331 -
Transplantation Aug 2016Alloreactive T lymphocytes are the primary mediators of allograft rejection. The size and diversity of the HLA-alloreactive T cell repertoire has thus far precluded the... (Review)
Review
Alloreactive T lymphocytes are the primary mediators of allograft rejection. The size and diversity of the HLA-alloreactive T cell repertoire has thus far precluded the ability to follow these T cells and thereby to understand their fate in human transplant recipients. This review summarizes the history, challenges, and recent advances in the study of alloreactive T cells. We highlight the historical development of assays to measure alloreactivity and discuss how high-throughput T cell receptor (TCR) sequencing-based assays can provide a new window into the fate of alloreactive T cells in human transplant recipients. A specific approach combining a classical in vitro assay, the mixed lymphocyte reaction, with deep T cell receptor sequencing is described as a tool to track the donor-reactive T cell repertoire for any specific HLA-mismatched donor-recipient pair. This assay can provide mechanistic insights and has potential as a noninvasive, highly specific biomarker for rejection and tolerance.
Topics: Allografts; Animals; Graft Rejection; Graft Survival; HLA Antigens; High-Throughput Nucleotide Sequencing; Histocompatibility; Histocompatibility Testing; Humans; Isoantigens; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Organ Transplantation; Phenotype; Predictive Value of Tests; Receptors, Antigen, T-Cell; Risk Factors; Signal Transduction; T-Lymphocytes; Treatment Outcome
PubMed: 26760572
DOI: 10.1097/TP.0000000000001064 -
Journal of Immunology (Baltimore, Md. :... May 2016Corneal transplantation is one of the most prevalent and successful forms of solid tissue transplantation. Despite favorable outcomes, immune-mediated graft rejection... (Review)
Review
Corneal transplantation is one of the most prevalent and successful forms of solid tissue transplantation. Despite favorable outcomes, immune-mediated graft rejection remains the major cause of corneal allograft failure. Although low-risk graft recipients with uninflamed graft beds enjoy a success rate ∼90%, the rejection rates in inflamed graft beds or high-risk recipients often exceed 50%, despite maximal immune suppression. In this review, we discuss the critical facets of corneal alloimmunity, including immune and angiogenic privilege, mechanisms of allosensitization, cellular and molecular mediators of graft rejection, and allotolerance induction.
Topics: Angiogenesis Inducing Agents; Animals; Corneal Transplantation; Graft Rejection; Humans; Immune Tolerance; Immunity, Cellular; Immunosuppression Therapy; Inflammation; Isoantigens; Risk; Transplantation Immunology
PubMed: 27183635
DOI: 10.4049/jimmunol.1600251 -
Current Opinion in Organ Transplantation Feb 2018This article reviews recent literature on the nature of extracellular vesicles released by allogeneic transplants and examine their role in T-cell alloimmunity involved... (Review)
Review
PURPOSE OF REVIEW
This article reviews recent literature on the nature of extracellular vesicles released by allogeneic transplants and examine their role in T-cell alloimmunity involved in rejection and tolerance of these grafts.
RECENT FINDINGS
Donor cells release extracellular vesicles, including exosomes, after transplantation of allogeneic organs and tissues. Consequently, recipient APCs take up these exosomes and present donor MHC antigens on their surface (allo-MHC cross-dressing) thus, activating some alloreactive T cells via a mechanism called semi-direct pathway of allorecognition. In addition, one study shows that exosomes carrying noninherited maternal antigens are associated with maternal microchimerism and tolerance in offspring. Finally, a few studies describe potential utilization of exosomes as modulators of alloimmunity and biomarkers of rejection in allotransplantation.
SUMMARY
Extracellular vesicles, including exosomes, released by allografts contribute to recognition of donor antigens by T cells after allotransplantation. This occurs through cross-dressing of recipient APCs with donor MHC antigens and subsequent activation of T cells, a process called semi-direct alloreactivity. The relevance of this phenomenon in rejection and tolerance of allografts and the potential utilization of exosomes as biomarkers in transplantation are discussed.
Topics: Allografts; Animals; Antigen Presentation; Exosomes; Graft Rejection; Histocompatibility Antigens; Humans; Isoantigens; Tissue Donors; Transplantation, Homologous
PubMed: 29189413
DOI: 10.1097/MOT.0000000000000489 -
Anais Da Academia Brasileira de Ciencias Sep 2009Neutrophil alloantigens are involved in a variety of clinical conditions including immune neutropenias, transfusion-related acute lung injury (TRALI), refractoriness to... (Review)
Review
Neutrophil alloantigens are involved in a variety of clinical conditions including immune neutropenias, transfusion-related acute lung injury (TRALI), refractoriness to granulocyte transfusions and febrile transfusion reactions. In the last decade, considerable progress has been made in the characterization of the implicated antigens. Currently, seven antigens are assigned to five human neutrophil antigen (HNA) systems. The HNA-1a, HNA-1b and HNA-1c antigens have been identified as polymorphic forms of the neutrophil Fcgamma receptor IIIb (CD16b), encoded by three alleles. Recently, the primary structure of the HNA-2a antigen was elucidated and the HNA-2a-bearing glycoprotein was identified as a member of the Ly-6/uPAR superfamily, which has been clustered as CD177. The HNA-3a antigen is located on a 70-95 kDa glycoprotein; however, its molecular basis is still unknown. Finally, the HNA-4a and HNA-5a antigens were found to be caused by single nucleotide mutations in the alphaM (CD11b) and alphaL (CD11a) subunits of the leucocyte adhesion molecules (beta2 integrins). Molecular and biochemical characterization of neutrophil antigenshave expanded our diagnostic tools by the introduction of genotyping techniques and immunoassays for antibody identification. Further studies in the field of neutrophil immunology will facilitate the prevention and management of transfusion reactions and immune diseases caused by neutrophil antibodies.
Topics: Autoantibodies; Genotype; Humans; Isoantigens; Neutrophils; Phenotype
PubMed: 19722024
DOI: 10.1590/s0001-37652009000300019 -
Human Immunology Aug 2019Lung transplant recipients (LTxRs) with acute or chronic rejection release circulating exosomes that mostly originate from donor lung tissue and express mismatched human... (Review)
Review
Lung transplant recipients (LTxRs) with acute or chronic rejection release circulating exosomes that mostly originate from donor lung tissue and express mismatched human leucocyte antigens (HLA) and lung-associated self-antigens (SAgs), Collagen-V and K alpha 1 Tubulin. During lung transplant (LTx), donor lungs often undergo injuries that increase the antigenicity of the transplanted organ. 30% of LTxRs also have pre-transplant antibodies (Abs) to HLA and lung SAgs, which may induce conditions that increase the risk of chronic lung allograft dysfunction (CLAD). Post-transplant, some recipients experience de novo development of Abs to mismatched donor HLA (donor-specific antibody [DSA]) and Abs to lung SAgs, which have been implicated in CLAD pathogenesis. Because most LTxRs who develop DSA also develop Abs to SAgs, some have suggested a synergistic relationship between alloimmunity and autoimmunity in CLAD immunopathogenesis. These processes likely occur from stress-induced exosome release. Exosomes carry allo-antigens, lung SAgs, several micro RNAs, proteasome, co-stimulatory molecules, and pro-inflammatory transcription factors-resulting in efficient antigen presentation by direct, semidirect, and indirect pathways, leading to immune responses to both allo-antigens and lung-associated SAgs. This review summarizes recent findings on the role of exosomes, and processes triggering immune responses to allo-antigens and lung SAgs that ultimately culminate in CLAD.
Topics: Animals; Antigen Presentation; Autoimmunity; Exosomes; Graft Rejection; HLA Antigens; Humans; Isoantigens; Lung Transplantation; Tissue Donors
PubMed: 30898684
DOI: 10.1016/j.humimm.2019.03.012