Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Adoptive Transfer of Induced-Regulatory T Cells Effectively Attenuates Murine Airway Allergic Inflammation.
Lan1, Qin, Xu2, Wei, Wang1, Julie, Fan3, Hui-Ming, Ryffel4, Bernhard, Shi2, Wei, Zheng5, Song G.
University of Southern California, Los Angeles, CA
The Saban Rrsearch Institute of Children's Hospital Los Angeles
Shanghai East Hospital, Tonji University, Shanghai, China
University and CNRS, 3b rue de la Ferollerie, F-45071 Orleans, France
USC Keck School of Medicine, Los Angeles, CA
Both nature (nTreg) and induced-regulatory T cells (iTreg) are potent regulator of autoimmune and allergic disorders. Defects in Treg cells have been reported in patients with allergic asthma, and therefore replenishment of Treg cells might attenuate asthma. Here we investigated if adoptive transfer of iTreg cells generated ex-vivo could attenuate lung and airway allergic inflammation in murine model of asthma.
Naïve CD4+ T cells purified from spleen in C57BL/6 mice, were activated with anti-CD3/CD28-coated beads (1 bead: 3 cells) and IL-2 (50U/ml), in the presence (iTregs) or absence (CD4 control) of TGF-b (2ng/ml). C57BL/6 mice were immunized with OVA mixed with aluminum hydroxide (day 0) and challenged with OVA control through an intranasal (i.n.) route for three consecutive days (days 25, 26, and 27) to generate an acute allergic asthma model. 5×106 of iTreg cells or control cells were intravenously injected into mice on day 22, three days before antigen challenge. Pathological changes in airway and lung were observed by H&E, Discombe's Solution and Periodic-Acid-Schiff (PAS) staining. The intracellular expression of Foxp3, IFN-g, IL-5 and IL-17 in CD4+ cells in spleens and draining lymph nodes was examined by flow cytometry. IgE in peripheral blood serum was measured by enzyme linked immunosorbent assay.
Immunized mice given iTreg cells just before antigen challenge displayed markedly reduced airway résistance, eosinophil recruitment, mucus hyper-production, airway remodeling and IgE levels. This therapeutic effect was associated with increase of Treg cells (CD4+FoxP3+) in the draining lymph nodes, and with reduction of Th1, Th2, and Th17 cell response as compared to untreated and non-Treg cell treated controls.
Therefore, adoptive transfer of iTreg reduces the allergic response, which might be a novel and promising therapeutic approach to treat severe asthma.
To cite this abstract, please use the following information:
Lan, Qin, Xu, Wei, Wang, Julie, Fan, Hui-Ming, Ryffel, Bernhard, Shi, Wei, et al; Adoptive Transfer of Induced-Regulatory T Cells Effectively Attenuates Murine Airway Allergic Inflammation. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :1924