NK Cell-Depleting Anti-Asialo GM1 Antibody Exhibits a Lethal Off-Target Effect on Basophils In Vivo.
Summary of "NK Cell-Depleting Anti-Asialo GM1 Antibody Exhibits a Lethal Off-Target Effect on Basophils In Vivo."
NK cells are innate immune lymphocytes and play a key role in both innate and adaptive immunity. Their pivotal functions in vivo have been illustrated in mice by means of their ablation with NK cell-depleting Abs, particularly anti-asialo GM1 (ASGM1). In this study, we show that the whole population of basophils constitutively expresses ASGM1 as well as CD49b (DX5) as does the NK cell population and was ablated in vivo by anti-ASGM1 as efficiently as by a basophil-depleting anti-FcεRIα Ab. Anti-ASGM1-mediated basophil depletion was operative as for NK cell depletion in various mouse strains, irrespective of NK1 allotype and MHC H2 haplotype, including C57BL/6, BALB/c, C3H, and A/J mice. These results identified basophils as a previously unrecognized target of anti-ASGM1-mediated cell depletion and raised concern about possible contribution of basophils, rather than or in addition to NK cells, to some of phenotypes observed in anti-ASGM1-treated mice. Indeed, regardless of the presence or absence of NK cells in mice, anti-ASGM1 treatment abolished the development of IgE-mediated chronic cutaneous allergic inflammation as efficiently as did the treatment with basophil-depleting Ab. Given the fact that basophils have recently been shown to play crucial roles in a variety of immune responses, our finding of the off-target effect on basophils issues a grave warning about the use of anti-ASGM1 and underscores the need for careful interpretation of phenotypes observed in anti-ASGM1-treated mice.
Affiliation
Department of Immune Regulation, Tokyo Medical and Dental University Graduate School, Tokyo 113-8519, Japan.
Journal Details
This article was published in the following journal.
Name: Journal of immunology (Baltimore, Md. : 1950)
ISSN: 1550-6606
Pages: 5766-71
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21490162
- DOI: http://dx.doi.org/10.4049/jimmunol.1100370
Medical and Biotech [MESH] Definitions
Antibody-dependent Cell Cytotoxicity
The phenomenon of antibody-mediated target cell destruction by non-sensitized effector cells. The identity of the target cell varies, but it must possess surface IMMUNOGLOBULIN G whose Fc portion is intact. The effector cell is a "killer" cell possessing Fc receptors. It may be a lymphocyte lacking conventional B- or T-cell markers, or a monocyte, macrophage, or polynuclear leukocyte, depending on the identity of the target cell. The reaction is complement-independent.
Fluorescent Antibody Technique
Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.
Fatty Acid Synthesis Inhibitors
Compounds that interfere with FATTY ACID SYNTHASE resulting in a reduction of FATTY ACIDS. This is a target mechanism in humans of some ANTINEOPLASTIC AGENTS and ANTI-OBESITY AGENTS and of some ANTI-INFECTIVE AGENTS which interfere with CELL WALL and CELL MEMBRANE formation.
Fluorescent Antibody Technique, Indirect
A form of fluorescent antibody technique commonly used to detect serum antibodies and immune complexes in tissues and microorganisms in specimens from patients with infectious diseases. The technique involves formation of an antigen-antibody complex which is labeled with fluorescein-conjugated anti-immunoglobulin antibody. (From Bennington, Saunders Dictionary & Encyclopedia of Laboratory Medicine and Technology, 1984)
Rosette Formation
The in vitro formation of clusters consisting of a cell (usually a lymphocyte) surrounded by antigenic cells or antigen-bearing particles (usually erythrocytes, which may or may not be coated with antibody or antibody and complement). The rosette-forming cell may be an antibody-forming cell, a memory cell, a T-cell, a cell bearing surface cytophilic antibodies, or a monocyte possessing Fc receptors. Rosette formation can be used to identify specific populations of these cells.
PubMed Articles
Rituximab in immunologic glomerular diseases.
Experimental data suggest that the B-cell antigen CD20 may play a significant role in the pathogenesis of many diseases including glomerular diseases. These and other findings underpin the central con...
The ability of transient immunosuppression with a combination of a non-depleting anti-CD4 (NDCD4) antibody and cyclosporine (CyA) to abrogate immune reactivity to both adeno-associated viral vector (A...
The B cell-depleting IgG1 monoclonal antibody rituximab can persistently suppress disease progression in some patients with autoimmune diseases. However, the mechanism underlying these long-term benef...
B cells and antibodies in multiple sclerosis pathogenesis and therapy.
B cells and antibodies account for the most prominent immunodiagnostic feature in patients with multiple sclerosis (MS), namely oligoclonal bands. Furthermore, evidence is accumulating that B cells an...
Anti-CD79 antibodies have been effective at targeting B cell lymphoma cells and depleting B cells in animal models. In order to engineer recombinant antibodies with additional effector functions in mi...
Clinical Trials
Anti-GD2 3F8 Antibody and Allogeneic Natural Killer Cells for High-Risk Neuroblastoma
The goal of this study is to see if it is safe and feasible to give chemotherapy, natural killer (NK) cells, and an antibody called 3F8. The NK cells must come from a family member who sha...
Expanded Access Study of Iodine-131 Anti-B1 Antibody
The primary objective of this study is to make Iodine-131 Anti-B1 Antibody more broadly available to patients. Secondary endpoints of the study will be to obtain additional information on...
The study purpose is to evaluate the clinical response to multidose administration of anti-Tac monoclonal antibody conjugated with 10 mCi 90Y in patients with Tac-expressing adult T-cell l...
The purpose of this study is to test the safety of Iodine-131 Anti-B1 Antibody followed by CHOP and to see what effects it has on patients with previously untreated mantel cell lymphoma.
Safety and Efficacy Study of GC1008 to Treat Renal Cell Carcinoma or Malignant Melanoma
The purpose of this study is to determine the safety, tolerability, pharmacokinetics and pharmacodynamics of GC1008, a human anti-transforming growth factor-beta (TGFβ) monoclonal antibod...
