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Tolerance-like mediated suppression by mesenchymal stem cells in patients with dust mite allergy–induced asthma  Simi Kapoor, MD, Shyam A. Patel, PhD,

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Presentation on theme: "Tolerance-like mediated suppression by mesenchymal stem cells in patients with dust mite allergy–induced asthma  Simi Kapoor, MD, Shyam A. Patel, PhD,"— Presentation transcript:

1 Tolerance-like mediated suppression by mesenchymal stem cells in patients with dust mite allergy–induced asthma  Simi Kapoor, MD, Shyam A. Patel, PhD, Saritha Kartan, MD, David Axelrod, MD, Eugenio Capitle, MD, Pranela Rameshwar, PhD  Journal of Allergy and Clinical Immunology  Volume 129, Issue 4, Pages (April 2012) DOI: /j.jaci Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 Flow diagram on inclusion/exclusion criteria. Shown are the methods used in enrolling subjects for the study. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 Specificity of DM antigen. A, Dose-response studies were performed with PBMCs from DM-sensitive subjects in proliferation assays. The data (disintegrations per minute [DPM]) are presented for 3 subjects, each tested in independent studies (mean ± SD, n = 9). ∗P < .01 versus other concentrations of DM. B, Time-course studies were performed with the optimum (5 μg/mL) DM level, as described in Fig 2, A. C, Proliferation assays were performed in the presence of DM, MSCs with optimum DM, or both. Four subjects were studied in each category, and each was studied in 3 independent experiments. The data are presented as means ± SDs (n = 12). Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig 3 Effects of MSCs on the proliferation of DM/tetanus toxoid-challenged PBMCs. PBMCs were assessed for proliferation in the presence or absence of DM (n = 7, A) or tetanus toxoid (n = 4, B), MSCs, or both. Each subject was assessed in 3 independent experiments, and the data are presented as SIs ± SDs. ∗P < .05 versus DM plus MSCs. ∗∗P < .05 versus tetanus toxoid plus MSCs. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig 4 Treg cells and DCs in DM-challenged PBMCs and MSCs. Multicolor flow cytometry was performed for Treg cells (A) and DCs (B) with PBMCs from subjects with allergic asthma and healthy subjects challenged with DM in the presence or absence of MSCs for 5 days. In the case of DCs, cells negative for CD64 were analyzed for CD86 and HLA-DR expression within the CD14+ and CD14− subsets. The studies in Fig 4, A were repeated in 2% FCS. The cells were analyzed for Tregs (not shown) and the media were quantitated for cytokines (C). The results are shown for allergic asthma, representing 3 experiments of all subgroups. ∗P > .05. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 Fig 5 Nonresponsiveness to DM by preconditioned PBMCs from allergic asthmatic subjects. PBMCs from subjects with DM sensitivity (n = 4), asthma (n = 4), or both were preincubated with MSCs. At day 5, the MSC-free PBMCs were studied in DM-challenged mitogen assays. Each subject was studied in 3 independent experiments. The results are presented as SIs ± SDs (n = 12). P < .05 versus preconditioned PBMCs without DM. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

7 Fig 6 Refractoriness of PBMCs from allergic asthmatic subjects after repeated challenge with low-dose DM and MSCs. PBMCs were challenged with low-dose DM in the presence of MSCs, as outlined in the Methods section. Parallel studies were performed in which PBMCs were challenged once with optimal DM in the presence or absence of MSCs. Cells with repeated DM challenges were washed and then re-exposed to optimal DM in proliferation assay. The results represent studies with 4 subjects, each performed in 3 independent experiments. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

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