Murine islet allograft tolerance upon blockade of the B-lymphocyte stimulator, BLyS/BAFF.
Transplantation 93(7):676 (2012)
Immunologic rejection is a major barrier to successful long-term outcomes in clinical transplantation. The importance of B lymphocytes-and their secretory products, alloantibodies-in the pathogenesis of allograft rejection is accepted. Furthermore, it is now clear that the dominant regulator of ...
Accumulation of intrahepatic islet amyloid in a nonhuman primate transplant model.
Endocrinology 153(4):1673 (2012)
Islet amyloid is hypothesized to play a role in nonimmunologic transplanted islet graft loss. We performed a quantitative histologic analysis of liver biopsies from intrahepatic islet grafts transplanted in streptozotocin-induced diabetic cynomolgus macaques. Seven animals treated with antithymo...
Acquisition of humoral transplantation tolerance upon de novo emergence of B lymphocytes.
Journal of Immunology 186(1):614 (2011)
A major obstacle to transplantation tolerance is humoral immunity. In this paper, we demonstrate that the intrinsic developmental propensity of the B lymphocyte compartment for acquisition of self-tolerance can be harnessed to induce humoral unresponsiveness to transplanted alloantigens. In the ...
In vivo BLyS/BAFF neutralization ameliorates islet-directed autoimmunity in nonobese diabetic mice.
Journal of Immunology 181(11):8133 (2008)
B lymphocytes are required for the pathogenesis of autoimmune diabetes in NOD mice. Previous studies established that a lymphopenic transitional (TR) B cell compartment reduces the competitive constraint on the entry of newly emerging TR B cells into the splenic follicle (FO), thereby disrupting...
CD4+ T cells recognizing a single self-peptide expressed by APCs induce spontaneous autoimmune arthritis.
Journal of Immunology 180(2):833 (2008)
We have examined processes leading to the spontaneous development of autoimmune inflammatory arthritis in transgenic mice containing CD4+ T cells targeted to a nominal Ag (hemagglutinin (HA)) and coexpressing HA driven by a MHC class II promoter. Despite being subjected to multiple tolerance mec...
B lymphocyte-directed immunotherapy promotes long-term islet allograft survival in nonhuman primates.
Nature Medicine 13(11):1295 (2007)
We found that an induction immunotherapy regimen consisting of rabbit anti-thymocyte globulin (Thymoglobulin) and the monoclonal antibody to CD20 rituximab (Rituxan) promoted long-term islet allograft survival in cynomolgus macaques maintained on rapamycin monotherapy. B lymphocyte reconstitutio...
B cell-mediated antigen presentation is required for the pathogenesis of acute cardiac allograft rejection.
Journal of Immunology 177(11):7715 (2006)
Acute allograft rejection requires the activation of alloreactive CD4 T cells. Despite the capacity of B cells to act as potent APCs capable of activating CD4 T cells in vivo, their role in the progression of acute allograft rejection was unclear. To determine the contribution of B cell APC func...
A glucose sensor role for glucokinase in anterior pituitary cells.
Diabetes 55(7):1923 (2006)
Enzymatic activity of glucokinase was demonstrated, quantitated, and characterized kinetically in rat and mouse pituitary extracts using a highly specific and sensitive spectrometric assay. A previously proposed hypothesis that the glucokinase gene might be expressed in the pituitary corticotrop...
T-reg mediated suppression of the allograft response in the draining lymph node.
Transplantation 81(7):1063 (2006)
We previously demonstrated that T-regs inhibit proliferation of graft-reactive T cells in the draining lymph node (DLN), suggesting that this site may be important for regulation. TCR transgenic mice (TS1) specific for viral hemagglutinin (HA) provided antigen-specific T cells for adoptive trans...
T-regs inhibit effector T cell accumulation to prolong allograft survival
Journal of the American College of Surgeons 201(3):S90 (2005)
Resistance to anti-CD45RB-induced tolerance in NOD mice: mechanisms involved.
Transplant International 17(5):261 (2004)
While great advances have been made in the success of islet transplantation to cure autoimmune diabetes, this protocol remains limited by our inability to induce donor-specific tolerance within the recipient. The profound resistance of the NOD mouse to tolerance-inducing regimens that are routin...
Structural and functional abnormalities in the islets isolated from type 2 diabetic subjects.
Diabetes 53(3):624 (2004)
Type 2 diabetic subjects manifest both disordered insulin action and abnormalities in their pancreatic islet cells. Whether the latter represents a primary defect or is a consequence of the former is unknown. To examine the beta-cell mass and function of islets from type 2 diabetic patients dire...
Helospectin-like immunoreactivity in the rat eye and pterygopalatine ganglion
Neuroscience Letters 183(1):108 (1995)
Helospectin I and II, nearly identical peptides isolated from lizard venom, show close sequence homology with vasoactive intestinal peptide (VIP). In mammals, the helospectins have been localized immunohistochemically to neurons of the brain, digestive tract and respiratory system, commonly...
Lens Development in a Dominant X-linked Congenital Cataract of the Mouse
Experimental Eye Research 57(5):587 (1993)
Xcat is a recently identified mouse mutation causing X-linked dominant congenital cataract. The mutation is of particular interest as a possible animal model for the human X-linked cataract syndrome. Using light microscopy, we examined the histological changes of mutant lenses at selected i...