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 Marcenaro, Claudia Cantoni, Silvia Pesce, Carola Prato, Daniela Pende, Sophie Agaugué, Lorenzo Moretta, Alessandro Moretta

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)4108-4116
Number of pages9
JournalBlood
Volume114
Issue number19
DOIs
Publication statusPublished - Nov 5 2009

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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