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J Zhang-Hoover, P Finn, J Stein-Streilein; ACAID Inducing DCs Block Both Th1 and Th2 Types of Immune Response-Mediated Pathogenesis in the Lung . Invest. Ophthalmol. Vis. Sci. 2002;43(13):885.
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Purpose: Anterior chamber associated immune deviation (ACAID) can be mimicked by intravenous inoculation of antigen-pulsed, TGFß2-treated (tolerogenic) antigen presenting cells. The mechanisms of tolerogenic dendritic cells (DCs) to suppress immune mediated pathology in the lung were explored. Methods: Tolerogenic DCs (5x105/mouse) were transferred (retroorbital) into pre-sensitized mice in either OVA-induced mouse asthma model (a Th2-mediated disease model) or Hapten Immune Pulmonary Interstitial Fibrosis (HIPIF) model (a Th1-mediated autoimmune fibrosis model). Airway hyperresponsiveness (AHR) was measured after methacholine (200 mg/ml) challenge using whole body Plethysmography. Cytokine production was measured by RT-PCR and ELISA assays. Fibrosis was detected by hydroxyproline assay. The presence of T regulatory cells was detected by their ability to block ear swelling in a contact hypersensitivity (CH) assay. Results: In OVA-asthma model, tolerogenic DC treatment reduced AHR, inflammatory cell infiltration, and cytokine (IL-4, IL-5, and IL-13, but not IFNγ) production in the asthma mice. In HIPIF model, Adoptive transfer of tolerogenic DCs blocked the development of immune mediated fibrosis in the HIPIF lung, and had no effect on the control lung. Enriched T cells from the draining lymph nodes of tolerogenic DC-treated HIPIF lung suppressed the effector phase of an ear swelling CH assay. Conclusion: Adoptively transferred ACAID-inducing-tolerogenic DCs block Th2-mediated pathogenesis in the OVA-asthma model and Th1-mediated autoimmune response in the HIPIF model. The suppression of the immune response in the lung of pre-sensitized mice by transferring tolerogenic DCs is mediated through the generation of T regulatory cells. The adaptation of ACAID from the eye to the lung indicates that mechanisms of tolerance used by the eye may lead to potential therapy for immune mediated diseases throughout the body, as well as the eye.
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