Mouse Invariant Monoclonal Antibody NKT14: A Novel Tool to Manipulate iNKT Cell Function In Vivo
| Autor: | Lennart K. A. Lundblad, David V. Serreze, Robert Mashal, Felix Scheuplein, Matthew E. Poynter, Jonathan E. Boyson, Deanna J. Lamont, Robert Schaub |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
medicine.drug_class
Receptors Antigen T-Cell lcsh:Medicine Nod Biology Monoclonal antibody Lymphocyte Depletion Antibodies Monoclonal Murine-Derived Mice Antigen Mice Inbred NOD medicine Animals lcsh:Science NOD mice Mice Inbred BALB C Multidisciplinary lcsh:R T-cell receptor Natural killer T cell Asthma 3. Good health Diabetes Mellitus Type 1 Immunology biology.protein Natural Killer T-Cells lcsh:Q Antibody Cell activation Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 10, Iss 10, p e0140729 (2015) |
| ISSN: | 1932-6203 |
| Popis: | Invariant Natural Killer T (iNKT) cells are a T cell subset expressing an invariant T Cell Receptor (TCR) that recognizes glycolipid antigens rather than peptides. The cells have both innate-like rapid cytokine release, and adaptive-like thymic positive selection. iNKT cell activation has been implicated in the pathogenesis of allergic asthma and inflammatory diseases, while reduced iNKT cell activation promotes infectious disease, cancer and certain autoimmune diseases such as Type 1 diabetes (T1D). Therapeutic means to reduce or deplete iNKT cells could treat inflammatory diseases, while approaches to promote their activation may have potential in certain infectious diseases, cancer or autoimmunity. Thus, we developed invariant TCR-specific monoclonal antibodies to better understand the role of iNKT cells in disease. We report here the first monoclonal antibodies specific for the mouse invariant TCR that by modifying the Fc construct can specifically deplete or activate iNKT cells in vivo in otherwise fully immuno-competent animals. We have used both the depleting and activating version of the antibody in the NOD model of T1D. As demonstrated previously using genetically iNKT cell deficient NOD mice, and in studies of glycolipid antigen activated iNKT cells in standard NOD mice, we found that antibody mediated depletion or activation of iNKT cells respectively accelerated and retarded T1D onset. In BALB/c mice, ovalbumin (OVA) mediated airway hyper-reactivity (AHR) was abrogated with iNKT cell depletion prior to OVA sensitization, confirming studies in knockout mice. Depletion of iNKT cells after sensitization had no effect on AHR in the conducting airways but did reduce AHR in the lung periphery. This result raises caution in the interpretation of studies that use animals that are genetically iNKT cell deficient from birth. These activating and depleting antibodies provide a novel tool to assess the therapeutic potential of iNKT cell manipulation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|