A5040973657- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- IL-33, ST2, and ILC Pathways
- Blood groups and transfusion
- Blood disorders and treatments
- Diabetes and associated disorders
- Immunodeficiency and Autoimmune Disorders
- Immune cells in cancer
- Platelet Disorders and Treatments
- Blood transfusion and management
- Reproductive System and Pregnancy
- Hemoglobinopathies and Related Disorders
- Erythrocyte Function and Pathophysiology
- RNA Interference and Gene Delivery
- Pancreatic function and diabetes
- Cancer Immunotherapy and Biomarkers
- Hematopoietic Stem Cell Transplantation
- Lymphoma Diagnosis and Treatment
- T-cell and Retrovirus Studies
- Neutropenia and Cancer Infections
- Pediatric health and respiratory diseases
- SARS-CoV-2 and COVID-19 Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Karolinska Institutet
2015-2024
Karolinska University Hospital
2013-2023
Integrated Cardio Metabolic Centre
2016-2022
IFC Research (United Kingdom)
2018
Canadian Blood Services
2018
Svenska Örtmedicinska Institute
2011
Imperial College London
2004
Institute of Genetics
1999
Walter and Eliza Hall Institute of Medical Research
1999
Inserm
1998-1999
Little is known about the events triggering lymphocyte invasion of pancreatic islets in prelude to autoimmune diabetes. For example, where islet-reactive T cells first encounter antigen has not been identified. We addressed this issue using BDC2.5 cell receptor transgenic mice, which express a recognizing natural islet beta antigen. In animals, activated were found only and lymph nodes draining them, there was close temporal correlation between node activation infiltration. When naive...
NK cells use a variety of receptors to detect abnormal cells, including tumors and their metastases. However, in the case melanoma, it remains be determined what specific molecular interactions are involved whether control metastatic progression and/or route dissemination. Here we show that human melanoma cell lines derived from LN metastases express ligands for natural cytotoxicity (NCRs) DNAX accessory molecule-1 (DNAM-1), two emerging key cancer recognition, but not group 2 member D...
Evidence has been accumulating that shows insulin-dependent diabetes is subject to immunoregulation. To determine whether cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) involved, we injected anti–CTLA-4 mAb into a TCR transgenic model of at different stages disease. When young mice, months before they would normally become diabetic, induced rapidly and essentially universally; this was not the result global activation lymphocytes, but did reflect much more aggressive cell infiltrate in...
The role of major histocompatibility complex (MHC) class I expression in control the sensitivity normal cells to natural killer (NK) was studied by use mutant mice made deficient for beta 2-microglobulin (beta 2m) through homologous recombination embryonal stem cells. T-cell blasts from 2m-deficient 2m -/-) were killed NK vitro, while +/- resistant. defect also affected effector cell repertoire: -/- failed kill blasts, they retained ability prototype target lymphoma YAC-1, although at...
Rejection of bone marrow grafts in irradiated mice is mediated by natural killer (NK) cells and controlled genes linked to the major histocompatibility complex (MHC). It has, however, not been possible identify or their products. An MHC class I (Dd) transgene introduced C57BL donors prevented rejection NK allogeneic F1 hybrid expressing Dd gene. Conversely, H-2Dd transgenic recipients acquired ability reject from but donors. These results provide formal evidence that are part a system...
Miscarriage and intrauterine growth restriction (IUGR) are devastating complications in fetal/neonatal alloimmune thrombocytopenia (FNAIT). We previously reported the mechanisms for bleeding diatheses, but it is unknown whether placental, decidual immune cells or other abnormalities at maternal-fetal interface contribute to FNAIT. Here we show that maternal responses fetal platelet antigens cause miscarriage IUGR associated with vascular pathologies murine FNAIT models. Uterine natural...
Neutropenia, as an isolated blood cell deficiency, is a feature of wide spectrum acquired or congenital, benign premalignant disorders with predisposition to develop myelodysplastic neoplasms/acute myeloid leukemia that may arise at any age. In recent years, advances in diagnostic methodologies, particularly the field genomics, have revealed novel genes and mechanisms responsible for etiology disease evolution opened new perspectives tailored treatment. Despite research field, real world...
The ability of murine NK cells to reject lacking self MHC class I expression results from an in vivo education process. To study the impact individual alleles on this process, we generated mice expressing single (Kb, Db, Dd, or Ld) combinations two more alleles. All rejected I–deficient cell–dependent way. Expression Kb Dd conveyed strong rejection cells, whereas Db Ld resulted weaker responses. educating weak ligands (Db and was further attenuated by introduction additional alleles, (Kb Dd)...
We have studied natural killer (NK) cell tolerance in a major histocompatibility complex (MHC) class I transgenic line, DL6, which the transgene product was expressed on only fraction of blood cells. In contrast with mice expressing same all cells, NK cells from mosaic failed to reject transgene-negative bone marrow or lymphoma grafts. However, they retained capability total missing-self phenotype, i.e., lacking also wild-type MHC molecules. Tolerance against demonstrated vitro, and could be...
The H-2Dd transgenic strain D8 on C57BL background was more resistant to subcutaneous challenge of RBL-5 lymphoma cells than B6 controls. direct role the antigen investigated by use (D8 x B6)F1 crosses and B6) backcrosses. latter showed cosegregation with regard Dd expression resistance, both which were inherited in a pattern consistent control single dominant gene. rejection potential mice appeared as strong that seen between MHC congenic (on B10 background) carrying H-2Dd. resistance could...
Treatment of H-2-deficient nonmetastatic B16 melanoma cells with physiological doses interferon gamma (IFN-gamma) reduced cellular growth in vitro but induced a shift to the lung-colonizing phenotype as assessed after intravenous injection treated cells. As little 1 antiviral unit recombinant IFN-gamma per ml form 3-40 pulmonary metastases each injected mouse, whereas 1000-fold higher concentration IFN-beta was required see similar effects. may induce cell-surface molecules that contribute...
Background. The risk of cutaneous squamous cell carcinoma (CSCC) is found to be substantially increased after organ transplantation. association with specific immunosuppressive regimens has been previously investigated, but results are not concordant. We aimed clarify the relationship between separate drugs, drug load, timing and post-transplant CSCC. Methods. A population-based nested case-control study was performed in Swedish transplantation cohort (n = 5931). All patients who developed...
Little is known about target organ-infiltrating NK cells in type 1 diabetes and other autoimmune diseases. In this study, we identified with a unique phenotype the pancreas of NOD mice. Pancreatic cells, localized to endocrine exocrine parts, were present before T during disease development did not require for their infiltration. Furthermore, or cell precursors, from spleen could traffic pancreas, where they displayed pancreatic phenotype. mouse strains shared phenotypic characteristics...
Natural killer (NK) cells hold great promise as a source for allogeneic cell therapy against hematological malignancies, including acute myeloid leukemia (AML). Current treatments are hampered by variability in NK subset responses, limitation which could be circumvented specific expansion of highly potent single immunoglobulin-like receptor (KIR)+NKG2C+ adaptive to maximize missing-self reactivity.We developed GMP-compliant protocol expand from cryopreserved derived select third-party...
Murine natural killer (NK) cells express inhibitory Ly49 receptors specific for major histocompatibility complex (MHC) class I molecules. We report that during interactions with in the environment, NK acquired MHC ligands from surrounding a Ly49-specific fashion and displayed them at cell surface. Ligand acquisition sometimes reached 20% of expression on cells, involved transfer entire protein to cell, was independent whether or not expressed ligand itself. also present indirect evidence...