Tolerance-like mediated suppression by mesenchymal stem cells in patients with dust mite allergy–induced asthma

• Published in: Journal of allergy and clinical immunology Vol. 129; no. 4; pp. 1094 - 1101
• Main Authors: Kapoor, Simi, Patel, Shyam A., Kartan, Saritha, Axelrod, David, Capitle, Eugenio, Rameshwar, Pranela
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.04.2012; Elsevier; Elsevier Limited
• Subjects: Adult; Allergens; Allergens - immunology; allergic asthma; Allergies; Allergy and Immunology; Animals; Asthma; Asthma - immunology; Asthma - metabolism; Biological and medical sciences; Bone marrow; CD25 antigen; CD4 antigen; Cell Proliferation; Cells, Cultured; Chronic obstructive pulmonary disease, asthma; Cytokines; Dendritic cells; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dermatophagoides; Dust; dust mite; dust mites; Enzyme-linked immunosorbent assay; Flow cytometry; Forkhead protein; Fundamental and applied biological sciences. Psychology; Fundamental immunology; gamma -Interferon; Humans; Hypersensitivity; Hypersensitivity - immunology; Immune response; Immune Tolerance - immunology; Immunopathology; Immunoregulation; Inflammation; interferon-gamma; Interleukin 10; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - metabolism; Lymphocyte Activation - immunology; Lymphocytes T; Medical sciences; Mesenchymal stem cells; Mesenchymal Stromal Cells - immunology; Mesenchymal Stromal Cells - metabolism; Mesenchyme; patients; Pneumology; proliferation; Pyroglyphidae - immunology; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Stem cells; T cells; T-lymphocytes; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Tetanus; therapeutics; Thymidine; tritium; Vaccines; Young Adult; dust mite; dendritic cells; proliferation; allergic asthma; SI; Treg; DM; T cells; MSC; Mesenchymal stem cells; DC; Mesenchymal stem cell; Dendritic cell; Stimulation index; Regulatory T; Cell proliferation; Allergy; Stem cell; Suppression; Mite; Immunology; Antigen presenting cell; T-Lymphocyte; Bronchus disease; Obstructive pulmonary disease; Human; Lung disease; Immunopathology; Respiratory disease; Tolerance; Mesenchymal cell; Asthma; Dust
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2011.10.048

Mesenchymal stem cells (MSCs) can suppress and enhance immune functions. MSCs show promise as off-the-shelf cellular therapy for several disorders, including inflammation. We investigated the effects of MSCs on the proliferation of PBMCs to allergic subjects (dust mite [DM]), allergic asthmatic subjects, or both. Proliferation was studied by using tritiated thymidine uptake with or without MSCs. The refractoriness of PBMCs to DM was examined after preconditioning with MSCs and after repeated challenge with low-dose DM. Flow cytometry was used to study regulatory T cells and dendritic cells (DCs), and ELISA was used to study cytokine production. Seven subjects with allergic asthma met the inclusion/exclusion criteria. MSCs significantly (P < .05) reduced the proliferation of 6 subjects with allergic asthma but not those with allergy alone. The effect was specific to the allergen because MSCs did not affect challenges to tetanus toxoid. There was no change in CD4/CD25/forkhead box protein 3–positive cells, although there were decreased IFN-γ and increased IL-10 levels. Numbers of mature DCs were increased 6-fold. Refractoriness to DM was achieved by means of repeated exposure to low-dose DM and MSCs and also MSC- preconditioned MSC. MSCs suppressed the proliferation of DM-challenged PBMCs from allergic asthmatic subjects but not from allergic subjects without asthma. MSCs blunted the maturation of DCs but not regulatory T cells. Repeated exposure to low-dose DM and MSCs, as well as preconditioning of PBMCs with MSCs, caused refractoriness to DM. These findings have implications for the use of MSCs in attenuation of the inflammatory responses to allergic triggers in asthmatic patients with off-the-shelf MSCs.