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Y. Jin, E.–M. Chong, L. Shen, L. Chen, Q. Zhang, R. Dana; The Role of Chemokine Receptor CCR7 in Corneal Antigen–Presenting Cells Trafficking . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1277.
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CCR7 has been implicated as being necessary for antigen–presenting cell (APC) trafficking to secondary lymphoid organs, including lymph nodes, to elicit an adaptive immune response. Our previous data have demonstrated that in the inflamed corneal microenvironment, CD11b+ and CD11C+ cells could express CCR7 to facilitate their interaction with afferent lymphatic vessels. Here, we studied the functional role of CCR7 in corneal APC trafficking using synegeneic models of corneal transplantation
We utilized two types of corneal grafts: (1) ovalbumin (OVA)–Alexa 488 100ug/2ul intrastomally–injected corneas, (2) cauterized corneas from green fluorescent protein (GFP) transgenic C57BL/6 background mice, placed orthotopically as grafts onto neovascularized syngeneic recipient beds. The ipsilateral draining lymph node cells were harvested at 48 hours after corneal transplantation. The expression of CCR7 on the migrated OVA–Alexa 488+ cells (both donor and host derived) or GFP+ cells (donor derived only) in the draining lymph nodes was determined by flow cytometry. Furthermore, we locally injected anti–CCL21 (SLC) neutrilizating antibodies after corneal transplantation and analyzed the changes in OVA–Alexa 488+ or GFP+ cell numbers in the recipient lymph nodes after antibody treatment.
48 hours after syngeneic corneal transplantation with GFP+ corneal grafts and OVA–Alexa 488+ corneal grafts, positive staining for CCR7 was identified on both migrated GFP+ cells and OVA–Alexa 488+ cells in the draining lymph nodes by flow ctometric analysis. Gating on these migrated cells, the percentage of CCR7+ cells was significantly higher than the percentage of CCR5+ cells and similar to the percentage of CD11C+ cells. The injection of neutralizating anti–CCL21 antibody significantly decreased the total number of these migrated cells in the draining lymph nodes at the early stage after cornea transplantation as compared to the isotype control.
Taken together, our results suggest that CCR7 can mediate both graft (donor)–derived and limbus (host)–derived APCs to migrate from the cornea to draining lymph nodes after corneal transplantation. Thus, CCR7 may play an important role in both the direct pathway and indirect pathway of allosensitization. Further studies are required to establish the relationship of CCR7–mediated APCs trafficking and alloimmunity in corneal transplantation.
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