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Blood, 5 November 2009, Vol. 114, No. 19, pp. 4108-4116.
Prepublished online as a Blood First Edition Paper on September 11, 2009; DOI 10.1182/blood-2009-05-222265.


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IMMUNOBIOLOGY

Uptake of CCR7 and acquisition of migratory properties by human KIR+ NK cells interacting with monocyte-derived DC or EBV cell lines: regulation by KIR/HLA-class I interaction

Emanuela Marcenaro1, Claudia Cantoni1,2, Silvia Pesce1, Carola Prato1, Daniela Pende3, Sophie Agaugué2,4, Lorenzo Moretta1,2, and Alessandro Moretta1

1 Dipartimento di Medicina Sperimentale and Centro di Eccellenza per le Ricerche Biomediche, Università degli Studi di Genova, Genova, Italy; 2 Istituto Giannina Gaslini, Genova, Italy; 3 Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy; and 4 Commissariat à l'Energie Atomique, Institut d'Imagerie Biomédicale (I2BM), Service de Recherche en Hémato-Immunologie, Hopital Saint-Louis, Paris, France

C-C chemokine receptor type 7 (CCR7) is a chemokine receptor playing a pivotal role in the induction of human natural killer (NK)–cell migration to lymph nodes. We show that "licensed" peripheral blood killer immunoglobulin-like receptor–positive (KIR+) NK-cell populations, as well as KIR+ NK-cell clones, de novo express CCR7 upon coculture with mature dendritic cells (mDCs) or Epstein-Barr virus (EBV)–transformed lymphoblastoid cell lines. As a consequence, they become capable of migrating in response to the CCR7-specific chemokines C-C chemokine ligand (CCL)–19 and/or CCL21. The acquisition of CCR7 by NK cells requires direct cell-to-cell contact, is detectable within a few minutes, and is due to receptor uptake from CCR7+ cells. This mechanism is tightly regulated by KIR-mediated recognition of human leukocyte antigen (HLA) class I as well as by adhesion molecules including leukocyte function-associated antigen 1 (LFA-1) and CD2. Analysis of NK-cell clones revealed that alloreactive (KIR-ligand mismatched) but not autologous NK cells acquire CCR7. These data have important implications in haploidentical hematopoietic stem cell transplantation (HSCT), in which alloreactive NK cells may acquire the ability to migrate to secondary lymphoid compartments (SLCs), where they can kill recipient antigen-presenting cells (APCs) and T cells thus preventing graft-versus-host (and host-versus-graft) reactions.


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