Induction of T cell adhesion to extracellular matrix or endothelial cell ligands by soluble or matrix-bound interleukin-7.
The putative effects of interleukin (IL)-7, operating in the context of extracellular matrix (ECM), on the adhesion of human T cells were examined. Recombinant human, IL-7 was found to bind ECM or fibronectin (FN) with IC50 values of 10-100 nM. Nanogram amounts of both soluble and, especially, FN- or ECM-bound IL-7, which differentially affected the morphologies of FN-adherent T cells, induced the adhesion of resting CD4+ and CD8+ T cells in dose-dependent and beta 1 integrin-dependent manners. Under static and flow conditions, soluble IL-7 also induced the binding of unstimulated T cells to vascular cell adhesion molecule-1, suggesting that this cytokine can also modulate integrin binding to endothelial cell ligands. The effects of affinity modulation by IL-7 of FN-specific beta 1 integrins depend on the presence of soluble FN, which inhibited T cell adhesion to FN induced by FN-bound IL-7 or by an integrin-specific affinity-modulating monoclonal antibody, but not by soluble IL-7 or phorbol 12-myristate 13-acetate. These findings provide an example of a major ECM integrin ligand, FN, which is capable of modulating its adhesive interactions with specific immune cells by associating with and presenting a cytokine in a bio-active state.
Ariel
A
A
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Hershkoviz
R
R
Cahalon
L
L
Williams
D E
DE
Akiyama
S K
SK
Yamada
K M
KM
Chen
C
C
Alon
R
R
Lapidot
T
T
Lider
O
O
D002448:Cell Adhesion / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D015851:Interleukin-7 / Q000494:pharmacology*; D007797:Laminin / Q000378:metabolism; D008024:Ligands; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D005353:Fibronectins; D019012:Integrin beta1; D015851:Interleukin-7; D007797:Laminin; D008024:Ligands; D019010:Vascular Cell Adhesion Molecule-1; D003094:Collagen