Purchase this article with an account.
Daniel R. Saban, Simona L. Schlereth, Hyun Soo Lee; Crucial Role For CCR7 Expression On Dendritic Cells In The Immunopathogenesis Of Experimental Allergic Conjunctivitis (AC). Invest. Ophthalmol. Vis. Sci. 2011;52(14):1203.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Elucidating chemokine mechanisms offers insight into the pathogenesis of ocular allergies, as they mediate dendritic cell (DC) mobilization from exposed sites to lymphocyte reservoirs located within lymphoid tissues to generate immunity. We therefore examined in AC the unknown role of chemokine receptor CCR7 on DCs.
Sorted T cells were harvested from wild-type (WT) C57BL/6 mice 14d after an ovalbumin (OVA; 100ug)/pertussis toxin (300ng)/alum (1mg) immunization. Naïve hosts were adoptively transferred with sorted T cells (10^6), and 1d later also received a subconjunctival (sconj) injection with cultivated bone marrow (BM)-derived DCs (10^5), or sham PBS control. Hosts were then challenged with OVA eye drops (50ug/ul) once daily for 12 days and post challenge slit-lamp evaluation was performed daily to follow development of clinical signs (e.g., chemosis, redness, tearing and lid edema). Additional parameters tested included mast cell infiltration, sera OVA specific IgE, and IL-4 and IL-13 levels to in vitro recall T cell stimulation.
Use of BMDCs were qualified in vitro by their capacity to capture OVA and proliferate T cells from immunized mice. In vivo qualification was demonstrated by instillation of FITC-conjugated OVA eye drops, which led to presence of sconj injected BMDCs that were FITC(+) in lymph nodes. Furthermore, OVA eye drops in adoptively transferred (WT T cells) mice with sconj injected BMDCs, versus sham injected PBS, showed significant augmentation of clinical signs (p<0.05). This was corroborated by a 2-fold increase in mast cell infiltration, 4-fold increase in IL-13 and IL-4 levels (p<0.05), and an 8-fold increase in sera IgE levels (p<0.05). Strikingly, this augmentation was completely reversed when OVA challenges were delivered to adoptively transferred hosts sconj injected with CCR7-/- BMDCs (rather than WT BMDCs), and this abrogation was consistent for all parameters tested. Moreover, this effect was similarly observed in adoptive transfer (of WT T cells) in CCR7-/- hosts, as sconj injection of CCR7-/- BMDCs (versus WT BMDCs) resulted in a significant reduction of AC clinical signs (p<0.05).
This model highlights the critical role of CCR7 on DCs in AC immunopathogenesis, and suggests that blocking CCR7 may serve as a much needed and effective modality in AC therapy.
This PDF is available to Subscribers Only