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Publication : The chemokine receptor CCR7 controls lymph node-dependent cytotoxic T cell priming in alloimmune responses.

First Author  Höpken UE Year  2004
Journal  Eur J Immunol Volume  34
Issue  2 Pages  461-70
PubMed ID  14768051 Mgi Jnum  J:121522
Mgi Id  MGI:3710393 Doi  10.1002/eji.200324690
Citation  Hopken UE, et al. (2004) The chemokine receptor CCR7 controls lymph node-dependent cytotoxic T cell priming in alloimmune responses. Eur J Immunol 34(2):461-70
abstractText  The chemokine receptor CCR7 and its ligands regulate migration and colocalization of T cells and mature dendritic cells to and within secondary lymphoid organs. The requirement of CCR7 in efficient priming of allospecific cytotoxic CD8(+) T cells is poorly characterized. Here, we demonstrate a role for CCR7 in the initiation of an alloimmune response and in the development of transplant rejection. Remarkably, in a model of acute allogeneic tumor rejection, CCR7(-/-) mice completely failed to reject subcutaneously injected MHC class I mismatched tumor cells and cytotoxic activity of allospecific T cells was severely compromised. When solid tumors derived from wild-type mice were transplanted, recipient CCR7(-/-) mice were capable of rejecting the allografts. In contrast, tumor allografts transplanted from CCR7(-/-) donors onto CCR7(-/-) recipients showed allograft survival up to 28 days, suggesting a critical function of CCR7 on donor-type passenger leukocytes in the initiation of cytotoxic CD8(+) T cell responses. In a heterotopic heart transplantation model CCR7 deficiency resulted in significantly prolonged but not indefinite allograft survival. Additional prolongation of graft survival was observed when hearts from CCR7(-/-) mice were used as donor organs. Our results define a key role for CCR7 in allogeneic T cell priming within the context of draining lymph nodes.
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