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

Item Type:Article
Title:The chemokine receptor CCR7 controls lymph node-dependent cytotoxic T cell priming in alloimmune responses
Creators Name:Hoepken, U.E. and Droese, J. and Li, J.P. and Joergensen, J. and Breitfeld, D. and 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 (U.S.A.)
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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