Treatment of Type 1 diabetes with anti-CD3 monoclonal antibody: induction of immune regulation?

Abstract:

:Anti-CD3 monoclonal antibodies (MAbs) were developed as a way of inducing immune suppression of T cells. More recent studies have indicated that anti-CD3 MAbs can affect immune responses by inducing immune regulation. We recently reported that a single course of treatment with a non-FcR binding anti-CD3 MAb, hOKT3gamma1(Ala-Ala), can lead to preservation of insulin production in patients with new-onset Type 1 diabetes for even beyond 1 yr after treatment. The sustained insulin production was accompanied by improvement in glucose control and reduced use of insulin. Our studies of the mechanism of the non-FcR binding anti-CD3 MAb indicate that the MAb delivers an activation signal to T cells resulting in disproportionate production of interleukin-10 (IL-10) relative to interferon-gamma(IFN-gamma) in vitro compared with FcR binding anti-CD3 MAb, and detectable levels of IL-10, IL-5, but rarely IFN-gamma or IL-2 in the serum after treatment. In addition, the drug induces a population of CD4+IL-10+ CCR4+ cells in vivo. Preclinical data suggest that anti-CD3 MAb induces a population of regulatory T cells that can prevent or lead to reversal of Type 1 diabetes. The induction of cells with a regulatory phenotype may account for the ability of anti-CD3 MAb to induce immune regulation.

journal_name

Immunol Res

journal_title

Immunologic research

authors

Herold KC,Taylor L

doi

10.1385/IR:28:2:141

subject

Has Abstract

pub_date

2003-01-01 00:00:00

pages

141-50

issue

2

eissn

0257-277X

issn

1559-0755

pii

IR:28:2:141

journal_volume

28

pub_type

杂志文章,评审
  • Following the TRAIL to apoptosis.

    abstract::Apoptosis, programmed cell death, eliminates injured or harmful cells. It can mediate its response through the actions of death ligands including TRAIL. TRAIL, a member of TNF superfamily, induces apoptosis of transformed cells through the action of death domain receptors DR-4 and DR5. It directly induces apoptosis th...

    journal_title:Immunologic research

    pub_type: 杂志文章,评审

    doi:10.1385/IR:35:3:249

    authors: Chaudhari BR,Murphy RF,Agrawal DK

    更新日期:2006-01-01 00:00:00

  • Bronchiolitis obliterans organizing pneumonia in patients with autoimmune rheumatic diseases.

    abstract::Bronchiolitis obliterans organizing pneumonia (BOOP) is defined by buds of granulation tissue within lung distal airspaces. The diagnosis requires the histopathologic evidence of organizing pneumonia along with a suggestive clinical and radiographic pattern. This disorder is characterized by a good response to cortico...

    journal_title:Immunologic research

    pub_type: 杂志文章,评审

    doi:10.1007/s12026-014-8607-z

    authors: Rojas CM,Borella E,Palma L,Ragozzino S,De Ramón E,Gomez-Huelgas R,Punzi L,Doria A

    更新日期:2015-02-01 00:00:00

  • Consequences of CXCL10 and IL-6 induction by the murine IFN-alpha1 transgene in ocular herpes simplex virus type 1 infection.

    abstract::Herpes simplex virus type 1 infection of the mouse eye results in an impressive inflammatory response culminating in the death of the animal or the establishment of a "latent" infection depending on a number of ill-defined variables that include components of the innate and adaptive immune system. The application of t...

    journal_title:Immunologic research

    pub_type: 杂志文章

    doi:10.1385/IR:30:2:191

    authors: Wickham S,Ash J,Lane TE,Carr DJ

    更新日期:2004-01-01 00:00:00

  • A multivalent vaccine for type 1 diabetes skews T cell subsets to Th2 phenotype in NOD mice.

    abstract::Previous studies by our group, using an experimental autoimmune thyroiditis (EAT) model in Strain 13 inbred guinea pigs, resulted in T cell-mediated delayed hypersensitivity; however, autoantibodies proved not to be cytotoxic to thyroid epithelial cells in the presence or absence of complement proteins. Albeit, T cell...

    journal_title:Immunologic research

    pub_type: 杂志文章

    doi:10.1007/s12026-011-8215-0

    authors: Lin MS,Tse HM,Delmastro MM,Bertera S,Wong CT,Lakomy R,He J,Sklavos MM,Coudriet GM,Pietropaolo M,Trucco MM,Piganelli JD

    更新日期:2011-08-01 00:00:00

  • Upregulation of long noncoding RNA TMEVPG1 enhances T helper type 1 cell response in patients with Sjögren syndrome.

    abstract::Long noncoding RNAs (lncRNA) play key roles in regulating autoimmunity and immunity balance. LncRNA TMEVPG1, which is encoded by a gene located near the Ifn gene, contributes to interferon gamma expression. We investigated the expression of TMEVPG1 in patients with Sjögren syndrome (SS) to determine its role in the pa...

    journal_title:Immunologic research

    pub_type: 杂志文章

    doi:10.1007/s12026-015-8715-4

    authors: Wang J,Peng H,Tian J,Ma J,Tang X,Rui K,Tian X,Wang Y,Chen J,Lu L,Xu H,Wang S

    更新日期:2016-04-01 00:00:00

  • The role of B cells and accessory cells in the neonatal response to TI-2 antigens.

    abstract::The neonate has an increased susceptibility to infection, in part owing to an inability to produce antibody to thymus-independent antigens such as bacterial polysaccharides (PS). This poor response to PS antigens is likely owing to multiple factors. Neonatal B cells are of an immature phenotype, as evidenced by cell-s...

    journal_title:Immunologic research

    pub_type: 杂志文章,评审

    doi:10.1385/IR:31:1:25

    authors: Landers CD,Chelvarajan RL,Bondada S

    更新日期:2005-01-01 00:00:00

  • Principles of homeostasis in governing virus activation and latency.

    abstract::The goal of our work is to understand, from the molecular to the organismal level, the principles that drive and sustain lifelong infection by viruses. These infectious agents live in a dynamic equilibrium (homeostasis) with their hosts in which both immune and nonimmune pathways contribute to viral homeostasis. Disru...

    journal_title:Immunologic research

    pub_type: 杂志文章,评审

    doi:10.1385/IR:21:2-3:219

    authors: Ghazal P,García-Ramírez J,González-Armas JC,Kurz S,Angulo A

    更新日期:2000-01-01 00:00:00

  • CD40-ligand in primate cardiac allograft and viral immunity.

    abstract::Our laboratory has studied the role of CD40 ligand (CD40L, CD154) in the primate immune response to allogenic and infectious challenges. We find that intensive early blockade of CD40L reliably attenuates acute rejection of primate cardiac allografts. Monotherapy fails to prevent late graft loss, which often occurs in ...

    journal_title:Immunologic research

    pub_type: 杂志文章

    doi:10.1385/IR:23:2-3:253

    authors: Pierson RN 3rd,Crowe JE Jr,Pfeiffer S,Atkinson J,Azimzadeh A,Miller GG

    更新日期:2001-01-01 00:00:00

  • Hematopoietic stem cell transplantation from matched unrelated donors in chronic granulomatous disease.

    abstract::We report on 12 patients with chronic granulomatous disease transplanted with hematopoietic stem cells from matched unrelated (n = 9) or matched sibling donors (n = 3). The most common infectious complication was pulmonary aspergillosis, which nine patients had previously developed. Only 5 of 12 individuals had normal...

    journal_title:Immunologic research

    pub_type: 杂志文章

    doi:10.1007/s12026-008-8068-3

    authors: Schuetz C,Hoenig M,Gatz S,Speth F,Benninghoff U,Schulz A,Debatin KM,Friedrich W

    更新日期:2009-01-01 00:00:00

  • The molecular basis of T cell differentiation.

    abstract::Our laboratory has studied the molecular basis of T helper cell differentiation. We have used reporter transgenic mice, selective hybridization techniques, and studies of cell signaling to show that a complex pattern of gene expression is reprogrammed as the decision is made to become either a Th1 or Th2 cell. Many of...

    journal_title:Immunologic research

    pub_type: 杂志文章,评审

    doi:10.1007/BF02786484

    authors: Flavell RA

    更新日期:1999-01-01 00:00:00

  • The genetic profiling of preferentially expressed genes in murine splenic CD8α+ dendritic cells.

    abstract::In the murine splenocytes, CD8α+ dendritic cells (abbreviated as 8+DC) and CD8α- dendritic cells (abbreviated as 8-DC) are identified with some vague features for each of them. 8+DCs but not 8-DCs cross-prime cytotoxic T cells in vivo. We aim to distinguish the two subtypes of DC based on gene expression profiling. Su...

    journal_title:Immunologic research

    pub_type: 杂志文章

    doi:10.1007/s12026-011-8237-7

    authors: Li T,Li WY,Bai HL,Ma HB,Zhang H,Zhu JM,Li XH,Huang HY,Ma YF,Ji XY

    更新日期:2011-10-01 00:00:00

  • Macrophage phenotype bioengineered by magnetic, genetic, or pharmacologic interference.

    abstract::In all eukaryotes, the cell shape depends on the actin filament cytoskeleton, which is regulated by the small GTPase RhoA. It is well known that the cell shape determines cell function and behavior. Inversely, any change in the cell behavior and/or function reverberates at the cell shape. In this review, we describe h...

    journal_title:Immunologic research

    pub_type: 杂志文章,评审

    doi:10.1007/s12026-019-9066-3

    authors: Wosik J,Suarez-Villagran M,Miller JH Jr,Ghobrial RM,Kloc M

    更新日期:2019-02-01 00:00:00

  • Strategies to enhance rituximab anti-tumor activity in the treatment of CD20-positive B-cell neoplasms.

    abstract::Rituximab is a chimeric monoclonal anti-CD20 antibody and was the first monoclonal antibody (mAb) therapy approved by FDA (Food and Drug Administration) for the treatment of B-cell lymphoma. It has revolutionized the treatment of patients with CD20-positive non-Hodgkin's lymphoma and CLL. Rituximab is currently being ...

    journal_title:Immunologic research

    pub_type: 杂志文章,评审

    doi:10.1007/s12026-009-8121-x

    authors: Riaz W,Hernandez-Ilizaliturri FJ,Czuczman MS

    更新日期:2010-03-01 00:00:00

  • Role of Ras/Raf/MEK/ERK signaling in physiological hematopoiesis and leukemia development.

    abstract::Recent research on hematological malignancies has shown that malignant cells often co-opt physiological pathways to promote their growth and development. Bone marrow homeostasis requires a fine balance between cellular differentiation and self-renewal; cell survival and apoptosis; and cellular proliferation and senesc...

    journal_title:Immunologic research

    pub_type: 杂志文章,评审

    doi:10.1007/s12026-010-8187-5

    authors: Chung E,Kondo M

    更新日期:2011-04-01 00:00:00

  • Unravelling the mechanisms of help for CD8+ T cell responses.

    abstract::CD8+ T cells are critically important for immune defense against many viral and bacterial pathogens, and are also key components of cancer immunotherapy. Help from CD4+ T cells is usually essential for optimal CD8+ T cell responses, driving the primary response, the survival of memory cells, and the generation of prot...

    journal_title:Immunologic research

    pub_type: 杂志文章,评审

    doi:10.1007/s12026-009-8102-0

    authors: Livingstone AM,Wilson EB,Ontiveros F,Wang JC

    更新日期:2009-12-01 00:00:00

  • Cytokines in posterior uveitis: an update.

    abstract::T helper (Th) lymphocytes differentiate into two distinct subsets--Th1 and Th2--as defined by functional abilities and cytokine profiles. The functional differences between Th subsets are explained primarily through the activities of the cytokines they secrete. Interferon-gamma (IFN-gamma) is the signature cytokine of...

    journal_title:Immunologic research

    pub_type: 杂志文章,评审

    doi:10.1385/IR:23:1:59

    authors: Singh VK,Rai G

    更新日期:2001-01-01 00:00:00

  • Requirements for activation of CD8+ murine T cells. I. Development of cytolytic activity.

    abstract::Cytolytic effector function fails to develop if proliferation of allospecific cytolytic T lymphocyte precursors is inhibited, but the requirements for generation of cytolytic activity have not been fully defined. In contrast, the cytolytic effector function of cytolytic T lymphocyte clones does not change during the c...

    journal_title:Immunologic research

    pub_type: 杂志文章

    doi:10.1007/BF02935614

    authors: Cronin DC 2nd,Lancki DW,Fitch FW

    更新日期:1994-01-01 00:00:00

  • Cross-linking the Leu-8 lymph node homing receptor on B cells inhibits immunoglobulin synthesis.

    abstract::About one half of circulating human B cells express the Leu-8 peripheral lymph node homing receptor that has been implicated in adhesion of lymphocytes and neutrophils to vascular endothelium. A novel and unique function of the Leu-8 antigen has been found in the present study: anti-Leu-8 monoclonal antibody directly ...

    journal_title:Immunologic research

    pub_type: 杂志文章,评审

    doi:10.1007/BF02919739

    authors: Murakawa Y,Strober W,James SP

    更新日期:1991-01-01 00:00:00

  • Multisubunit receptors in the immune system and their association with the cytoskeleton: in search of functional significance.

    abstract::Various multisubunit receptors of the immune system share similarities in structure and induce closely related signal transduction pathways upon ligand binding. Examples include the T cell antigen receptor (TCR), the B cell antigen receptor (BCR), and the high-affinity receptor for immunoglobulin E (Fc epsilon RI). Al...

    journal_title:Immunologic research

    pub_type: 杂志文章,评审

    doi:10.1007/BF02918171

    authors: Caplan S,Baniyash M

    更新日期:1995-01-01 00:00:00

  • Organ distribution of histones after intravenous infusion of FITC histones or after sepsis.

    abstract::Histones appear in plasma during infectious or non-infectious sepsis and are associated with multiorgan injury. In the current studies, intravenous infusion of histones resulted in their localization in major organs. In vitro exposure of mouse macrophages to histones caused a buildup of histones on cell membranes foll...

    journal_title:Immunologic research

    pub_type: 杂志文章

    doi:10.1007/s12026-015-8628-2

    authors: Fattahi F,Grailer JJ,Jajou L,Zetoune FS,Andjelkovic AV,Ward PA

    更新日期:2015-03-01 00:00:00

  • Suppression of HLA expression by lentivirus-mediated gene transfer of siRNA cassettes and in vivo chemoselection to enhance hematopoietic stem cell transplantation.

    abstract::Current approaches for hematopoietic stem cell (HSC) and organ transplantation are limited by donor and host-mediated immune responses to allo-antigens. Application of these therapies is limited by the toxicity of preparative and post-transplant immunosuppressive regimens and a shortage of appropriate HLA-matched dono...

    journal_title:Immunologic research

    pub_type: 杂志文章

    doi:10.1007/s12026-008-8088-z

    authors: Hacke K,Falahati R,Flebbe-Rehwaldt L,Kasahara N,Gaensler KM

    更新日期:2009-01-01 00:00:00

  • Preclinical validation of interleukin 6 as a therapeutic target in multiple myeloma.

    abstract::Studies on the biologic and molecular genetic underpinnings of multiple myeloma (MM) have identified the pleiotropic, pro-inflammatory cytokine, interleukin-6 (IL-6), as a factor crucial to the growth, proliferation and survival of myeloma cells. IL-6 is also a potent stimulator of osteoclastogenesis and a sculptor of...

    journal_title:Immunologic research

    pub_type: 杂志文章,评审

    doi:10.1007/s12026-014-8528-x

    authors: Rosean TR,Tompkins VS,Tricot G,Holman CJ,Olivier AK,Zhan F,Janz S

    更新日期:2014-08-01 00:00:00

  • Human neutrophil peptide-1 decreases during ageing in selected Mexican population.

    abstract::Antimicrobial peptide innate immunity plays a central role in the susceptibility to infectious diseases, as has been described extensively in different settings. However, the role that these molecules play in the immunity mediated by polymorphonuclear phagocytes as part of the innate immunity of ageing individuals has...

    journal_title:Immunologic research

    pub_type: 杂志文章

    doi:10.1007/s12026-015-8689-2

    authors: Rivas-Santiago B,Castañeda-Delgado JE,de Haro-Acosta J,Torres-Juarez F,Frausto-Lujan I,Marin-Luevano P,González-Amaro R,Enciso-Moreno JA

    更新日期:2016-04-01 00:00:00

  • Immunobiology of tumor necrosis factor receptor superfamily.

    abstract::The proteins of the tumor necrosis factor (TNF) receptor superfamily are a group of cell-surface receptors critically involved in the maintenance of homeostasis of the immune system. By interacting with their corresponding ligands, these receptors either induce cell death or promote cell survival of immune cells. The ...

    journal_title:Immunologic research

    pub_type: 杂志文章,评审

    doi:10.1385/IR:26:1-3:323

    authors: Zhou T,Mountz JD,Kimberly RP

    更新日期:2002-01-01 00:00:00

  • A translational bridge to cancer immunotherapy: exploiting costimulation and target antigens for active and passive T cell immunotherapy.

    abstract::Building on significant advances in basic tumor immunology over the past decade, current translational efforts to develop novel antitumor T cell therapeutics continue to accelerate. Both passive T cell immunotherapy (e.g., adoptive T cell transfusions) and active immunotherapy (e.g., vaccination) may eventually become...

    journal_title:Immunologic research

    pub_type: 杂志文章,评审

    doi:10.1385/IR:27:2-3:341

    authors: Vonderheide RH,June CH

    更新日期:2003-01-01 00:00:00

  • Diverse immune mechanisms may contribute to the survival benefit seen in cancer patients receiving hyperthermia.

    abstract::There is increasing documentation of significant survival benefits achieved in cancer patients treated with hyperthermia in combination with radiation and/or chemotherapy. Most evidence collected regarding the mechanisms by which hyperthermia positively influences tumor control has centered on in vitro data showing th...

    journal_title:Immunologic research

    pub_type: 杂志文章,评审

    doi:10.1007/s12026-009-8115-8

    authors: Peer AJ,Grimm MJ,Zynda ER,Repasky EA

    更新日期:2010-03-01 00:00:00

  • A mouse model for infectious mononucleosis.

    abstract::Epstein-Barr virus (EBV) is a ubiquitous human gamma-herpesvirus that establishes life-long latency and is associated with lymphoproliferative disorders and the development of several malignancies. EBV infection is frequently, but not always, associated with the development of a syndrome termed infectious mononucleosi...

    journal_title:Immunologic research

    pub_type: 杂志文章,评审

    doi:10.1385/IR:25:3:201

    authors: Flaño E,Woodland DL,Blackman MA

    更新日期:2002-01-01 00:00:00

  • Effect of CD40/CD40L signaling on IL-10-producing regulatory B cells in Chinese children with Henoch-Schönlein purpura nephritis.

    abstract::The aim of the present study was to examine the role and mechanism of interleukin-10 (IL-10)-producing regulatory B cells (B10 cells) in the pathogenesis of Henoch-Schönlein purpura nephritis (HSPN). We examined the percentage of B10 cells, CD19+CD24hiCD38hi B cells, CD19+CD24hiCD27+ B cells, Th17 cells, and T regulat...

    journal_title:Immunologic research

    pub_type: 杂志文章

    doi:10.1007/s12026-016-8877-8

    authors: Yang B,Tan X,Xiong X,Wu D,Zhang G,Wang M,Dong S,Liu W,Yang H,Li Q

    更新日期:2017-06-01 00:00:00

  • Microglial cells and Parkinson's disease.

    abstract::Chronic inflammation mediated by microglial cells is the fundamental process contributing to the death of dopamine (DA)-producing neurons in the brain. Production of inflammatory products by these microglial cells characterizes the slow destructive process in Parkinson's disease (PD). The activation of microglial cell...

    journal_title:Immunologic research

    pub_type: 杂志文章

    doi:10.1007/s12026-008-8018-0

    authors: Qian L,Flood PM

    更新日期:2008-01-01 00:00:00

  • Immunologic states of autoimmune diseases.

    abstract::The etiology and immunologic states of autoimmune diseases have mainly been discussed without consideration of extrathymic T cells, which exist in the liver, intestine, and excretion glands. Because extrathymic T cells are autoreactive and are often simultaneously activated along with autoantibody-producing B-1 cells,...

    journal_title:Immunologic research

    pub_type: 杂志文章,评审

    doi:10.1385/IR:33:1:023

    authors: Abo T,Kawamura T,Watanabe H

    更新日期:2005-01-01 00:00:00