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

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Item Type:	Article
Title:	The chemokine receptor CCR7 controls lymph node-dependent cytotoxic T cell priming in alloimmune responses
Creators Name:	Höpken, U.E., Droese, J., Li, J.P., Joergensen, J., Breitfeld, D., Zerwes, H.G. and Lipp, M.
Abstract:	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.
Keywords:	Dendritic Cell Migration, Homeostatic Chemokine Receptor, Lymphocyte Homing, Secondary Lymphoid Organs, Transplantation, Animals, Mice
Source:	European Journal of Immunology
ISSN:	0014-2980
Publisher:	Wiley
Volume:	34
Number:	2
Page Range:	461-470
Date:	1 January 2004
Official Publication:	https://doi.org/10.1002/eji.200324690
PubMed:	View item in PubMed

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