Involvement of CXCR4 and IL-2 in the homing and retention of human NK and NK T cells to the bone marrow and spleen of NOD/SCID mice.

Abstract

Human natural killer (NK) and NK T cells play an important role in allogeneic bone marrow (BM) transplantation and graft-versus-leukemia (GVL) effect. The mechanisms by which these cells home to the BM and spleen are not well understood. Here we show that treatment of these cells with pertussis toxin and neutralizing antibodies to the chemokine receptor CXCR4 inhibited homing of the cells to the BM, but not the spleen, of NOD/SCID mice. The retention of NK and NK T cells within the spleen and BM was dependent on Galphai signaling and CXCR4 function. The chemokine receptors CXCR4 and CXCR3 are expressed predominantly on the cell surface of NK T cells. Following activation with interleukin-2 (IL-2), the levels of CXCR4 on NK and NK T cells decreased significantly. Treatment of cells with IL-2 inhibited their migration in response to CXCL12 and their homing and retention in the BM and spleen of NOD/SCID mice. In contrast to CXCR4, the expression levels of the chemokine receptor CXCR3 and the migration of cells in response to CXCL9 and CXCL10 increased after IL-2 treatment. Thus, down-regulation of CXCR4 and up-regulation of CXCR3 may direct the trafficking of cells to the site of inflammation, rather than to hematopoietic organs, and therefore may limit their alloreactive potential.

• Authors: Katia Beider, Arnon Nagler, Ori Wald, Suzanna Franitza, Michal Dagan-Berger, Hanna Wald, Hilla Giladi, Stefan Brocke, Jacob Hanna, Ofer Mandelboim, Merav Darash-Yahana, Eithan Galun, Amnon Peled
• Journal: Blood (Blood) Vol. 102 Issue 6 Pg. 1951-8 (Sep 15 2003) ISSN: 0006-4971 [Print] United States
• PMID: 12730102 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies
• CXCR3 protein, human
• Cxcr3 protein, mouse
• Interleukin-2
• Receptors, CXCR3
• Receptors, CXCR4
• Receptors, Chemokine

Topics

• Animals
• Antibodies (pharmacology)
• Bone Marrow (immunology)
• Bone Marrow Cells (immunology)
• Bone Marrow Transplantation (immunology)
• Graft vs Host Disease (immunology)
• Humans
• In Vitro Techniques
• Interleukin-2 (immunology)
• Killer Cells, Natural (immunology)
• Mice
• Mice, Inbred NOD
• Mice, SCID
• Receptors, CXCR3
• Receptors, CXCR4 (immunology)
• Receptors, Chemokine (immunology)
• Specific Pathogen-Free Organisms
• Spleen (cytology, immunology)
• T-Lymphocytes (immunology)