Migration of Vδ1 and Vδ2 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, Maria Raffaella Zocchi

Research output: Contribution to journalArticle

Abstract

We show that HIV-1-infected patients have Increased concentrations of circulating Vδ1 T cells (2.2%-9.0% of T lymphocytes; healthy donors, 1.0%-2%) and, in some instances, Vδ2 T cells (3.5%-4.8% vs 2.0%-3.3%). In these patients, both Vδ1 and Vδ2 T cells are CXCR3 +CXCR4+, whereas in healthy donors CXCR4 was preferentially expressed on Vδ1 T lymphocytes, γδ T cells transmigrated across endothelial monolayers, in response to interferon-γ -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 Vδ1 CXCR3+ cells, whereas Vδ2 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.

Original languageEnglish
Pages (from-to)2205-2213
Number of pages9
JournalBlood
Volume103
Issue number6
DOIs
Publication statusPublished - Mar 15 2004

ASJC Scopus subject areas

  • Hematology

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