β-Agonist enhances type 2 T-cell survival and accumulation

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Presentation transcript:

β-Agonist enhances type 2 T-cell survival and accumulation Matthew J. Loza, PhD, Stephen P. Peters, MD, PhD, Susan Foster, PhD, Islam U. Khan, PhD, Raymond B. Penn, PhD Journal of Allergy and Clinical Immunology Volume 119, Issue 1, Pages 235-244 (January 2007) DOI: 10.1016/j.jaci.2006.09.019 Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Accumulation of IL-13+ and IFN-γ+ T cells. Before (day 0) or after culture for 5 days with IL-2 and CD3 plus CD28 mAb or 6 days with IL-2, PBLs were stimulated for cytokine production. A, Representative experiment of day 0 expression of IL-13 and IFN-γ. Numbers (B) and proportions (C) of total (CD3+), IL-13+, and IFN-γ+ T cells for cultured cells were normalized to the respective day 0 values (= 100%) and plotted for each subject tested (bars = median). ∗P < .05 for median versus day 0. PE, Phycoerythrin; FITC, fluorescein isothiocyanate. Journal of Allergy and Clinical Immunology 2007 119, 235-244DOI: (10.1016/j.jaci.2006.09.019) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Effects of β-agonist and PGE2 on accumulation of T-cell subsets. A and B, PBLs were cultured for 5 days with IL-2 and CD3 plus CD28 mAb or 6 days with IL-2 plus vehicle, ISO, or PGE2 and then stimulated for cytokine production. Percentage change in numbers (Fig 2, A) and proportions (Fig 2, B) of total (CD3+), IL-13+, and IFN-γ+ T cells are plotted for each subject tested. P < .05: ∗from control condition (reflecting 0 on y-axes); †between ISO- versus PGE2-treated conditions. C, Representative analysis of VASP phosphorylation in T cells after indicated stimulation. Journal of Allergy and Clinical Immunology 2007 119, 235-244DOI: (10.1016/j.jaci.2006.09.019) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Mechanisms for modulation of T-cell subset accumulation. CFSE-labeled PBLs were cultured for 6 days with IL-2 (A-C) or 5 days with IL-2 and CD3 plus CD28 mAb (A, D, and E) plus vehicle, ISO, or PGE2 and then stimulated for cytokine production. For the vehicle conditions, minimum progenitor numbers versus the respective number of IL-13+(top) and IFN-γ+(bottom) T cells in the original (day 0) population for each subject tested are shown (Fig 3, A). Percentage changes relative to the vehicle-treated conditions for average division numbers and progenitor numbers versus percentage change in numbers of cytokine-positive T cells, with symbols plotted for each subject tested, are shown (Fig 3, B-E). Journal of Allergy and Clinical Immunology 2007 119, 235-244DOI: (10.1016/j.jaci.2006.09.019) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 β-Agonist–mediated reduction in apoptosis in type 2 T cells. Apoptosis was analyzed in T-cell subsets during culture with IL-2 plus vehicle or ISO. A, Representative analysis for vehicle condition on day 3. B, Average percentage of Annexin V–positive T cells for each subject (left) and mean for each T-cell population (right). C, Percentage change for ISO relative to vehicle condition for each subject (left) and mean for each T-cell population (right). D, Mean percentage decrease in proportion of Annexin V–positive cells in the CRTH2+ T-cell population for ISO relative to vehicle conditions for each day of culture. P < .05: ∗between indicated populations; †from vehicle condition. Journal of Allergy and Clinical Immunology 2007 119, 235-244DOI: (10.1016/j.jaci.2006.09.019) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 PKA dependence of modulation of IL-13+ T-cell accumulation. A, Freshly isolated PBLs from patients with SLE were cultured for 6 days with IL-2 plus vehicle, PGE2, or ISO and then stimulated for cytokine production. The percentage change in IL-13+ T cells is reported for each subject tested. B, VASP phosphorylation in T cells from patients with SLE is indicated. Numbers in histograms are the percentage change in proportion of IL-13+ T cells for IL-2–stimulated cultures. Journal of Allergy and Clinical Immunology 2007 119, 235-244DOI: (10.1016/j.jaci.2006.09.019) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 6 Proposed regulation of T-cell numbers. Even though IL-13+ T cells proliferate slightly less in the β-agonist condition, IL-13+ cells accumulate to greater numbers than in the IL-2–only condition because of reduced apoptosis. In the PGE2 condition decreases in both proliferation and IL-13+ cell progenitor number contribute to a reduction in the final IL-13+ cell number. Journal of Allergy and Clinical Immunology 2007 119, 235-244DOI: (10.1016/j.jaci.2006.09.019) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions