Abstract:
:The migration of immunocytes within the extracellular matrix (ECM) is influenced by the activation state of the incoming cell and its responses to the presence of chemokines and cytokines. We studied the regulatory role of TGF-beta1 on T cell homing to secondary lymphatic organs, such as the spleen, and chemotaxis within an ECM-like environment in using an ECM-like 3-dimensional gel system designed to follow the migration of individual leukocytes along chemokine gradients in real time. The numbers of migrating naive, but not memory T cells toward SDF-1alpha markedly increased after pre-incubating the cells with TGF-beta1 (0.25 ng/ml) for 24 h. The mechanisms underlying TGFbeta1-modulated migration involve the up-regulation of the expression of the SDF-1alpha receptor CXCR4, the enhancement of the SDF-1alpha-induced actin polymerization, and increased phosphorylation of Pyk2, a focal adhesion kinase involved in integrin-mediated lymphocyte migration, adhesion and interactions with ECM. Interestingly, priming of naive human T cells with TGF-beta1 increased homing of these cells to the spleen of NOD/SCID mice in a CXCR4-dependent manner. We propose that the effect of TGF-beta1 on the chemotaxis of naive T cells may be important in the locomotion of naive T cells toward SDF-1alpha-rich niches.
journal_name
Eur J Immunoljournal_title
European journal of immunologyauthors
Franitza S,Kollet O,Brill A,Vaday GG,Petit I,Lapidot T,Alon R,Lider Odoi
10.1002/1521-4141(200201)32:1<193::AID-IMMU193>3.0keywords:
subject
Has Abstractpub_date
2002-01-01 00:00:00pages
193-202issue
1eissn
0014-2980issn
1521-4141journal_volume
32pub_type
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