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J. Zhang-Hoover, J. Stein-Streilein; ACAID Inducing DCs Generate CD8+ T Regulatory Cells that Block Autoimmune Mediated-fibrosis in the Lung . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1057.
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Purpose: The suppression of Th1 mediated immune responses by anterior chamber associated immune deviation (ACAID) can be reproduced ex vivo by inoculation of TGFbeta2-treated, antigen-pulsed (tolerogenic) antigen presenting cells intravenously. The mechanisms of tolerogenic dendritic cells (DCs) to suppress autoimmune mediated-fibrosis in the lung were explored. Methods: Tolerogenic DCs (5x105/mouse) or enriched splenic T cells or CD4+/CD8+ T cells (4 x 106 or equivalent/mouse) were transferred (i.v.) into pre-sensitized mice in Hapten Immune Pulmonary Interstitial Fibrosis (HIPIF) model (a Th1-mediated autoimmune fibrosis model). Fibrosis was detected by hydroxyproline assay. An ear swelling contact hypersensitivity (CH) assay was used to detect regulatory cells. Results: 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 lung draining lymph nodes and spleens of tolerogenic DC-treated, but not control DC-treated HIPIF mice suppressed the effector phase of an ear swelling CH assay and development of fibrosis in another set of HIPIF mice. Depletion of CD8+ T cells removed the suppressive effect of splenic T cells on the ear swelling CH response, as well as the development of fibrosis in the HIPIF lung. Conclusions: ACAID-inducing-tolerogenic DCs generate T regulatory cells in both the spleen and lung draining lymph nodes that can be adoptively transferred to suppress the autoimmune response and the subsequent fibrosis development in the lung of pre-sensitized HIPIF mice. 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.
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