Differential usage of VLA-4 and CXCR4 by CD3+CD56+ NKT cells and CD56+CD16+ NK cells regulates their interaction with endothelial cells.
The mechanism that regulates the preferential accumulation of NKT cells in the BM is unknown. The BM endothelium constitutively expresses selectins, the integrin ligands VCAM-1 and ICAM-1, and the chemokine CXCL12. Both NK and NKT subsets of cells exhibited similar tethering and rolling interactions on both P-selectin and E-selectin and expressed similar levels of the integrins, VLA-4 and LFA-1. Although NKT cells express higher levels of CXCR4 than NK cells, CXCL12 (the ligand for CXCR4) rapidly stimulates similar levels of adhesion of NK and NKT cells to VCAM-1 and ICAM-1. In both subsets, the arrest on VCAM-1 was dependent on high affinity VLA-4 and the homing of these cells to the BM of NOD/SCID was VLA-4-dependent. However, as opposed to the situation for NK cells, CXCL12 preferentially triggers, under shear flow, the rolling on VCAM-1 and transendothelial migration of NKT cells. Moreover, over-expression of high levels of CXCR4 on the YT NK cell line enables them to migrate in response to CXCL12. This study therefore suggests an important role for CXCR4 levels of expression and for VLA-4 in regulating the accumulation of NKT cells in the BM.
Franitza
Suzanna
S
Hadassah University Hospital, Goldyne Savad Gene Therapy Institute, Jerusalem, Israel.
Grabovsky
Valentin
V
Wald
Ori
O
Weiss
Ido
I
Beider
Katia
K
Dagan
Michal
M
Darash-Yahana
Merav
M
Nagler
Arnon
A
Brocke
Stefan
S
Galun
Eithan
E
Alon
Ronen
R
Peled
Amnon
A
D000818:Animals; D017252:CD3 Complex / Q000378:metabolism; D019002:CD56 Antigen / Q000378:metabolism; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism*; D039041:Integrin alpha4beta1 / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000378:metabolism*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D051379:Mice; D019718:Receptors, CXCR4 / Q000378:metabolism*; D017452:Receptors, IgG / Q000378:metabolism; D019087:Selectins / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism
D017252:CD3 Complex; D019002:CD56 Antigen; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D039041:Integrin alpha4beta1; D016169:Lymphocyte Function-Associated Antigen-1; D019718:Receptors, CXCR4; D017452:Receptors, IgG; D019087:Selectins; D018799:Intercellular Adhesion Molecule-1