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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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