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Blood, 15 March 2004, Vol. 103, No. 6, pp. 2205-2213.
Prepublished online as a Blood First Edition Paper on November 20, 2003; DOI 10.1182/blood-2003-08-2928.

Submitted August 27, 2003
Accepted November 5, 2003
Migration of V 1 and V 2 T cells in response to CXCR3 and CXCR4 ligands in healthy donors and HIV-1 infected patients: competition by HIV-1 TAT
Alessandro Poggi*, Roberta Carosio, Daniela Fenoglio, Sabrina Brenci, Giuseppe Murdaca, Maurizio Setti, Francesco Indiveri, Silvia Scabini, Elisabetta Ferrero, and Maria Raffaella Zocchi
Laboratory of Immunlogy, National Cancer Research Institute, Genoa, Italy
CEBR, University of Genoa, Genoa, Italy
Department of Internal Medicine, University of Genoa, Genoa, Italy
Laboratory of Tumor Immunology, Scientific Institute San Raffaele, Milan, Italy
* Corresponding author; email: poggi{at}vega.cba.unige.it.
We show that HIV-1-infected patients have increased circulating V 1 T cells (2.2-9.0% of T lymphocytes; healthy donors: 1.0-2%) and, in some instances, also V 2 T cells (3.5-4.8% vs 2.0-3.3%). In these patients, both V 1 and V 2 T cells are CXCR3+CXCR4+, while in healthy donors CXCR4 was preferentially expressed on V 1 T lymphocytes.  T cells transmigrated across endothelial monolayers, in response to interferon- inducing protein-10 (IP-10/CXCL10) and/or stromal-derived factor-1 (SDF-1/CXCL12) according to the expression of the specific receptors CXCR3 and CXCR4. Interestingly, 6Ckine/SLC/CCL21 was more effective than IP-10/CXCL10 on V 1 CXCR3+ cells, while V 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 upon 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, due to the cystein-rich domain of the protein, which contains CXC and CC chemokine-like sequences.

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