Blood, 2004-03, Vol.103 (6), p.2205-2213
2004
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- Autor(en) / Beteiligte
- Titel
- Migration of V delta 1 and V delta 2 T cells in response to CXCR3 and CXCR4 ligands in healthy donors and HIV-1-infected patients: competition by HIV-1 Tat
- Ist Teil von
- Blood, 2004-03, Vol.103 (6), p.2205-2213
- Ort / Verlag
- United States
- Erscheinungsjahr
- 2004
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- We show that HIV-1-infected patients have increased concentrations of circulating V delta 1 T cells (2.2%-9.0% of T lymphocytes; healthy donors, 1.0%-2%) and, in some instances, V delta 2 T cells (3.5%-4.8% vs 2.0%-3.3%). In these patients, both V delta 1 and V delta 2 T cells are CXCR3+CXCR4+, whereas in healthy donors CXCR4 was preferentially expressed on V delta 1 T lymphocytes. gamma delta T cells transmigrated across endothelial monolayers, in response to interferon-gamma-inducing protein-10 (IP-10/CXCL10), stromal cell-derived factor-1 (SDF-1/CXCL12), or both, according to the expression of the specific receptors CXCR3 and CXCR4. Interestingly, 6Ckine/SLC/CCL21 was more effective than IP-10/CXCL10 on V delta 1 CXCR3+ cells, whereas V delta 2 CXCR3+ cells were driven more efficiently by IP-10/CXCL10. IP-10/CXCL10- and SDF-1/CXCL12-induced transmigration was dependent on phosphoinositide-3 kinase (PI-3K), as demonstrated by the use of the specific blockers wortmannin and LY294002 and by the activation of the downstream serine kinase Akt/PKB on ligation of CXCR3 and CXCR4. Occupancy of CXCR3, but not of CXCR4, led to CAMKII activation; accordingly, the CAMKII inhibitors KN62 and KN93 decreased IP-10/CXCL10- but not SDF-1/CXCL12-driven transmigration. Finally, HIV-1 Tat, which is present in the serum of HIV-1-infected patients, interferes with the chemotactic activity of these chemokines because of the cysteine-rich domain of the protein, which contains CXC and CC chemokine-like sequences.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0006-4971DOI: 10.1182/blood-2003-08-2928Titel-ID: cdi_proquest_miscellaneous_71696578
- Format
- –
- Schlagworte
- Adult, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Calcium-Calmodulin-Dependent Protein Kinases - metabolism, Cell Movement - immunology, Cells, Cultured, Chemokine CXCL10, Chemokine CXCL12, Chemokines, CXC - metabolism, Endothelium, Vascular - cytology, Female, Gene Products, tat - chemistry, Gene Products, tat - metabolism, HIV Infections - immunology, HIV-1, Humans, Ligands, Male, Middle Aged, Phosphatidylinositol 3-Kinases - metabolism, Protein Binding - immunology, Protein Structure, Tertiary, Receptors, Chemokine - chemistry, Receptors, Chemokine - metabolism, Receptors, CXCR3, Receptors, CXCR4 - metabolism, T-Lymphocyte Subsets - cytology, T-Lymphocyte Subsets - metabolism, T-Lymphocyte Subsets - virology, tat Gene Products, Human Immunodeficiency Virus, Umbilical Veins - cytology