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CJ Calder, N Taylor, J Liversidge, AD Dick; Respiratory Tract Dendritic Cells prime Th1 T Cell Responses: Implications for Intranasal Tolerance Therapy in Experimental Autoimmune Uveoretinitis (EAU) . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1545.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Suppression of experimental autoimmune uveoretinitis (EAU) can be achieved by a single intranasal application of autoantigen. One proposed mechanism is that the respiratory tract dendritic cell (RTDC) modulates T cell responses, generating either a Th2 or T regulatory phenotype within the local drainage lymph node. Therefore we wished to assess (i) the behaviour of directly isolated RTDC to maturation signals and antigen priming and (ii) whether retinal antigen pulsed RTDC could prime T cell responses in vivo. Methods: RTDC were isolated from perfused bronchopulmonary tissue of C57BL/6 mice following enzyme digestion, density centrifugation and subsequently magnetic bead or flow cytometric cell sorting to achieve either RTDC-enriched or ≷95% purified RTDC population. Phenotype and cytokine (ELISA) profiles were determined either directly ex vivo or following maturation overnight alone or in combination with GM-CSF, IL-4, LPS, TNFα and IRBP peptide 1-20. Antibody production was assessed following naive or primed RTDC transfer. Results: Directly isolated RTDC are of an immature phenotype (iRTDC) displaying low levels of co-accessory molecules and low levels of IL-12-production. Following maturation signals RTDC generated IL-12 p40 (mRTDC). Antigen-primed RTDC elicited both Th1 and Th2 antibody responses in vivo. Conclusions: Bronchorespiratory iRTDC behave as spleen DC following maturation signals. When pulsed with peptide that is known to induce EAU, mRTDC are capable of driving a Th1 response. Results imply that tolerance is not dependent on a specific RTDC behaviour but likely to be as a result of microenvironment of drainage lymph nodes as well as route of antigen delivery.
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