Purpose: To identify the role of chemokine receptor 6 (D6) expression by dendritic cells (DCs) and its role in corneal transplant immunity. Methods: Flow cytometry analysis was used to assess the expression level of the D6 chemokine receptor in different leukocyte populations and DC maturation following lipopolysaccharides (LPS) stimulation of bone marrow-derived DCs isolated from wild-type (WT) or D6-/- mice (C57BL/6 background). Mixed-lymphocyte reactions and delayed-type hypersensitivity assays were performed with bone marrow-derived DCs from WT or D6-/- mice to evaluate T-cell al-loreactivity. Adoptive transfer experiments with T cells from WT or D6-/- hosts with BALB/c corneal allografts were performed. Graft opacity was assessed over an 8-week period, and graft survival was plotted using Kaplan-Meier survival curves. Results: Expression of the D6 chemokine receptor was signifcantly higher in DCs compared to other leukocyte subpopu-lations, including neutrophils, lymphocytes, and monocytes/macrophages. LPS challenge of D6-/- bone marrow-derived DCs elicited signifcantly lower levels of major histocompatibility complex II and costimulatory molecules (CD40, CD80, and CD86) compared to WT bone marrow-derived DCs, indicating the role of the D6 chemokine receptor in DC maturation. Further, DCs isolated from D6-/- mice induced less T-cell proliferation (p≤0.001) and interferon-gamma production in T cells of draining lymph nodes compared to WT mice following corneal transplantation (p≤0.001). Moreover, adoptively transferred T cells from D6-/- corneal transplanted mice to WT mice led to impaired graft rejection, compared to the hosts that received T cells from the WT transplanted mice. Conclusions: We demonstrated D6 chemokine receptor expression by DCs and identifed its critical function in multiple aspects of DC biology, including maturation and consequent elicitation of alloreactive T-cell responses that are responsible for corneal allograft rejection.
|Original language||English (US)|
|Number of pages||9|
|State||Published - Dec 16 2013|
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