A5085662667- Renal Transplantation Outcomes and Treatments
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Organ Transplantation Techniques and Outcomes
- Diabetes and associated disorders
- Renal Diseases and Glomerulopathies
- Pancreatic function and diabetes
- Transplantation: Methods and Outcomes
- Immune Response and Inflammation
- Polyomavirus and related diseases
- Reproductive System and Pregnancy
- Cytomegalovirus and herpesvirus research
- Psoriasis: Treatment and Pathogenesis
- Immune cells in cancer
- Diabetes Management and Research
- Phagocytosis and Immune Regulation
- Angiogenesis and VEGF in Cancer
- Galectins and Cancer Biology
- Cell Adhesion Molecules Research
- COVID-19 Clinical Research Studies
- Chemokine receptors and signaling
- SARS-CoV-2 and COVID-19 Research
- Cancer Immunotherapy and Biomarkers
- Liver Disease and Transplantation
- Pregnancy and Medication Impact
Northwestern University
2013-2024
Northwestern Medicine
2022
University of Chicago
2018
Saudi Center for Organ Transplantation
2014
Brigham and Women's Hospital
2003-2013
Harvard University Press
2003-2013
Harvard University
2004-2013
Johns Hopkins University
2008
Juntendo University
2008
Johns Hopkins Medicine
2008
Programmed death-1 (PD-1) receptor, an inhibitory costimulatory molecule found on activated T cells, has been demonstrated to play a role in the regulation of immune responses and peripheral tolerance. We investigated this pathway development autoimmune diabetes. PD-1 or PD-L1 but not PD-L2 blockade rapidly precipitated diabetes prediabetic female nonobese diabetic (NOD) mice regardless age (from 1 10-wk-old), although it was most pronounced older mice. By contrast, cytotoxic...
Experimental autoimmune encephalomyelitis (EAE) is mediated by autoantigen-specific T cells dependent on critical costimulatory signals for their full activation and regulation. We report that the programmed death-1 (PD-1) pathway plays a role in regulating peripheral tolerance murine EAE appears to be major contributor resistance of disease induction CD28-deficient mice. After immunization with myelin oligodendrocyte glycoprotein (MOG) there was progressive increase expression PD-1 its...
Fetal survival during gestation implies that tolerance mechanisms suppress the maternal immune response to paternally inherited alloantigens. Here we show inhibitory T cell costimulatory molecule, programmed death ligand 1 (PDL1), has an important role in conferring fetomaternal allogeneic pregnancy model. Blockade of PDL1 signaling murine resulted increased rejection rates concepti but not syngeneic concepti. was cell- B cell-dependent because PDL1-specific antibody treatment caused fetal...
T-bet plays a crucial role in Th1 development. We investigated the of development allograft rejection an established MHC class II–mismatched (bm12 into B6) model chronic vasculopathy (CAV). Intriguingly, and contrast to IFN-γ−/− mice that are protected from CAV, T-bet−/− recipients develop markedly accelerated accompanied by early severe vascular inflammation vasculopathy, infiltration predominantly IL-17–producing CD4 T cells. Concurrently, exhibit helper type 1 (Th1)–deficient environment...
Imbalance in the regulatory immune mechanisms that control intestinal cellular and bacterial homeostasis may lead to induction of detrimental inflammatory signals characterized humans as bowel disease. Induction proinflammatory cytokines (i.e., IL-12) induced by dendritic cells (DCs) expressing pattern recognition receptors skew naive T helper 1 polarization, which is strongly implicated mucosal autoimmunity. Recent studies show ability probiotic microbes treat prevent numerous disorders,...
Abstract There is considerable interest in therapeutic transfer of regulatory T cells (Tregs) for controlling aberrant immune responses. Initial clinical trials have shown the safety Tregs hematopoietic stem cell transplant recipients and subjects with juvenile diabetes. Our hypothesis that infusion(s) may induce tolerance thus avoiding long-term use toxic immunosuppressive agents cause increased morbidity/mortality. Towards testing our hypothesis, we conducted a phase I dose escalation...
Key Points Posoleucel was generally safe, well tolerated, and associated with a greater reduction of BK viremia compared placebo. occurred coincident an increase in the circulating frequency virus–specific T cells posoleucel recipients. The presence persistence confirmed by T-cell receptor variable β sequencing. Background Kidney transplant recipients virus infection are at risk developing virus–associated nephropathy, allograft rejection, subsequent graft loss. There no approved treatments...
T regs that expand in human colon cancer have proinflammatory properties and contribute to tumor progression.
T cell Ig mucin 1 (TIM-1) plays an important role in regulating immune responses autoimmune and asthma models, it is expressed on both Th1 Th2 cells. Using antagonistic TIM-1–specific antibody, we studied the of TIM-1 alloimmunity. A short course antibody monotherapy prolonged survival fully MHC-mismatched vascularized mouse cardiac allografts. This prolongation was associated with inhibition alloreactive preservation responses. treatment more effective Th1-type cytokine–deficient Stat4–/–...
Significance Statement Ischemia-reperfusion AKI (IR-AKI) is common and causes significant morbidity. Effective treatments are lacking. However, preclinical studies suggest that inhibition of angiopoietin-Tie2 vascular signaling promotes injury, whereas activation Tie2 protective. We show kidney ischemia leads to increased levels the endothelial-specific phosphatase endothelial protein tyrosine (VE-PTP; PTPRB), which inactivates Tie2. Activation through VE-PTP deletion, or delivery a novel...
Background— Allograft vasculopathy is a major limiting factor in the long-term success of cardiac transplantation. T cells play critical role initiation allograft rejection and vasculopathy. The negative T-cell costimulatory pathway PD-1:PDL1/PDL2 (programmed death-1:programmed death ligand-1/2) plays an important regulating alloimmune responses. We investigated recipient versus donor PD-1 ligands pathogenesis with emphasis on tissue expression this response vivo. Methods Results— used...
Chemokines play a major role in the recruitment of leukocytes inflammation and regulation T helper 1 (Th1)/Th2 immune responses. These mechanisms have been recognized to be important pathogenesis renal ischemia-reperfusion (I/R) injury. The interaction CXC chemokine receptor 3 (CXCR3) with its ligands is key pathogenic pathway promoting enhancing Th1 After induction ischemia mouse model ischemia, an increase intrarenal expression CXCR3 was observed. Compared wild-type (WT) mice,...
The ability to induce durable transplantation tolerance predictably and consistently in the clinic is a highly desired but elusive goal. Progress hampered by lack of appropriate experimental models which study resistance tolerance. Here, we demonstrate that T helper 1-associated box 21 transcription factor (Tbet) KO recipients exhibit allograft specifically mediated IL-17-producing CD8 (T17) cells. Neutralization IL-17 facilitates long-term cardiac survival with combined cell co-stimulation...
Significance T-cell exhaustion limits the immune response against chronic infections and tumors. Reinvigorating exhausted T cells promotes clearance of There are several ongoing clinical trials to harness potential reinvigorated for treatment tumors by reversing exhaustion. However, mechanisms leading unknown. Further, role in transplantation or autoimmunity is not defined. Here we show that impaired leukocyte recruitment leads CD4 as a novel mechanism transplant tolerance. Strategies...
The objective of this study was to validate the performance Tutivia, a peripheral blood gene expression signature, in predicting early acute rejection (AR) post–kidney transplant. Recipients living or deceased donor kidney transplants were enrolled nonrandomized, prospective, global, and observational (NCT04727788). main outcome validation area under curve (AUC) Tutivia vs serum creatinine at biopsy alone, + biopsy. Of 151 transplant recipients, mean cohort age 53 years old, 64% male. There...
Regulatory T cells (Tregs) actively regulate alloimmune responses and promote transplantation tolerance. Thymoglobulin, a rabbit polyclonal antithymocyte globulin (ATG), is widely used induction therapy in clinical organ that depletes peripheral cells. However, resistance to tolerance seen with certain T-cell depleting strategies attributed alterations the balance of naive, memory Tregs. The exact mechanism action ATG its effects on homeostasis between Tregs T-effector-memory (Tem) are...
Background Despite significant nephrotoxicity, calcineurin inhibitors (CNIs) remain the cornerstone of immunosuppression in solid organ transplantation. We, along with others, have reported tolerogenic properties anti-thymocyte globulin (ATG, Thymoglobulin®), evinced by its ability both to spare Tregs from depletion vivo and, when administered at low, non-depleting doses, expand ex vivo. Clinical trials investigating B7/CD28 blockade (LEA29Y, Belatacept) kidney transplant recipients proven...
Solid organ transplantation mobilizes myeloid cells, including monocytes and macrophages, which are central protagonists of allograft rejection. However, cells can also be functionally reprogrammed by perioperative costimulatory blockade to promote a state tolerance. Transplantation tolerance holds promise reduce complications from chronic immunosuppression long-term survival in transplant recipients. We sought identify different mediators performing single-cell RNA sequencing acute...
ABSTRACT. Islet transplantation is becoming an accepted therapy to cure type I diabetes mellitus. The exact mechanisms of islet allograft rejection remain unclear, however. In vivo CD4+ and CD8+ T cell-depleting strategies genetically altered mice that did not express MHC class or II antigens were used study the allorecognition effector pathways in different strains mice, including autoimmunity-prone nonobese diabetic (NOD) mice. BALB/c depended on both cells. C57BL/6 cells could eventually...
CD160 is a cell surface molecule expressed by most NK cells and approximately 50% of CD8+ cytotoxic T lymphocytes. Engagement MHC class-I directly triggers costimulatory signal to TCR-induced proliferation, cytokine production effector functions. The role in alloimmunity unknown. Using newly generated fusion protein (CD160Ig) we examined the novel mediating CD4+ or driven allograft rejection. CD160Ig inhibits alloreactive proliferation IFN-γ vitro, particular absence CD28 costimulation....