Induction of longstanding immunologic tolerance is essential for survival of transplanted organs and tissues. Despite recent advances in immunosuppression protocols, allograft damage inflicted by antibody specific for donor organs continues to represent a major obstacle to graft survival. Here we report that activation of regulatory CD8 T cells (CD8 Treg) that recognize the Qa-1 class Ib major histocompatibility complex (MHC), a mouse homolog of human leukocyte antigen-E (HLA-E), inhibits antibody-mediated immune rejection of heart allografts. We analyzed this response using a mouse model that harbors a point mutation in the class Ib MHC molecule Qa-1, which disrupts Qa-1 binding to the T cell receptor (TCR)-CD8 complex and impairs the CD8 Treg response. Despite administration of cytotoxic T lymphocyte antigen 4 (CTLA-4) immunoglobulin (Ig), Qa-1 mutant mice developed robust donor-specific antibody responses and accelerated heart graft rejection. We show that these allo-antibody responses reflect diminished Qa-1-restricted CD8 Treg-mediated suppression of host follicular helper T cell-dependent antibody production. These findings underscore the critical contribution of this Qa-1/HLA-E-dependent regulatory pathway to maintenance of transplanted organs and suggest therapeutic approaches to ameliorate allograft rejection.
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http://dx.doi.org/10.1073/pnas.1918950117 | DOI Listing |
Infect Disord Drug Targets
December 2024
Department of Pharmaceutical Chemistry, Dadasaheb Balpande College of Pharmacy, Nagpur, 440037, Maharashtra, India.
As of early October 2020, the COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, resulted in approximately 35 million cases and one million fatalities worldwide. Systemic lupus erythematosus (SLE) is an autoimmune disease marked by the generation of pathogenic autoantibodies and a lack of tolerance to nuclear self-antigens. Hypocomple-mentemia, or an abnormal blood complement deficit, is a reliable predictor of infection in SLE patients.
View Article and Find Full Text PDFVet Parasitol
December 2024
Department of Microbiology, Swedish Veterinary Agency, Uppsala SE 751 89, Sweden.
Coccidiosis, infection with protozoan parasites of genus Eimeria, is a major problem in poultry husbandry world-wide. The disease is currently managed by coccidiostats and live vaccines, but these approaches are not sustainable. Hence, it is important to identify new means to control the infection and/or ameliorate its detrimental effects on gut health.
View Article and Find Full Text PDFBiomaterials
December 2024
Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, 250012, China.
Tumor cells transmit various immunosuppressive signals and induce a dysfunctional state in T cells, which essentially leads to immune escape and tumor progression. However, developing effective strategies to counteract the domestication of T cells by tumor cells remains a challenge. Here, we prepared pH-responsive lipid nanoparticles (NL/PLDs) co-loaded with PCSK9 shRNA, lonidamine (LND), and low-dose doxorubicin (DOX).
View Article and Find Full Text PDFJ Exp Clin Cancer Res
December 2024
Department of Oncology, Molecular Biotechnology Center "G. Tarone", University of Torino, Piazza Nizza 44, Torino, 10126, Italy.
Background: Malignant pleural mesothelioma (MPM) is a highly chemo-refractory and immune-evasive tumor that presents a median overall survival of 12-14 months when treated with chemotherapy and immunotherapy. New anti-tumor therapies as well as the concomitant reactivation of immune destruction are urgently needed to treat patients with this tumor. The aim of this work is to investigate the potential effect of ecteinascidin derivatives as lurbinectedin as new first-line treatment option in MPM, alone and in combination with immunotherapy.
View Article and Find Full Text PDFInt Immunopharmacol
December 2024
Department of Immunology, Tarbiat Modares University, Tehran, Iran.
Sulfur mustard (SM) induced pulmonary disorder is a heterogeneous disease characterized by uncontrolled inflammatory immune responses. In this cross-sectional study carried out in Isfahan-Iran, our objective was to thoroughly evaluate the clinical health and peripheral blood leukocyte profiles of adult veterans exposed to SM 25-30 years. In total, 361 people were studied in two groups, 287 chemical veterans with pulmonary complications and 64 healthy individuals as a control group.
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