AEGiS-14IAC: SDF-1 production by dendritic cells and regulation of CXCR4 in T lymphocytes.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

SDF-1 production by dendritic cells and regulation of CXCR4 in T lymphocytes.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. TuOrA1137)

Bermejo M, Serrano JM, Alonso J, de Pablos JL, Gamallo C, Arenzana F, Alcami J
Centro Nacional de Microbiologia. Instituto de Salud Carlos III, Majadahonda, Madrid, Spain

BACKGROUND: Emergence of X4 HIV strains occurs late in the course of HIV infection, suggesting that a selective pressure interpheres with the switch from CCR5 to CXCR4 coreceptor tropism. We hypothesized that SDF-1 production could be involved in this process and to this aim we have analyzed the expression of SDF-1 in lymph nodes and cultured dendritic cells. We have also studied the expression and regulation of CXCR4 in resting and activated peripheral blood lymphocytes.

METHODS: Characterization of SDF-1 producing cells in paraffin-embedded sections in normal tonsils and lymph nodes from HIV infected patients at different clinical stages was analyzed by immunohistochemistry and in situ hybridization techniques, using specific antibodies against SDF-1, CD1a and dendritic cells antigens. Expression of SDF-1 was assessed in an "in vitro" model of dendritic cell differentiation using flow cytometry, western blot and RT-PCR techniques. PBLs were activated with PHA, soluble OKT3 antibody, PMA, SEA or SDF-1. Membrane and cytosolic CXCR4 expression was measured at different times using flow cytometry and confocal laser scanning microscopy.

RESULTS: SDF-1 was widely expressed in endothelial cells and also by dendritic cells (CD1a+) in tonsil cripts and in the parafollicular compartment of lymph nodes. In contrast, neither resting nor activated T-cells produced SDF-1. Only about 20% of freshly isolated lymphocytes expressed CXCR4 on the cell surface whereas in 80% of resting lymphocytes CXCR4 was located intracellularly.

CONCLUSIONS: These results suggest that downregulation of CXCR4 in peripheral T-lymphocytes could be related to interaction with SDF-1 in endothelial and dendritic cells. The presence of SDF-1 producing cells in the parafollicular T-cell region could account for the low propagation of X4 HIV strains in early stages of infection, in which lymph node structure is still conserved.

Keywords: AEGIS, Chemokines, CXC, Dendritic Cells, T-Lymphocytes, Receptors, HIV, Phytohemagglutinins, HIV, HIV Infections, Social Control, Formal, Anti-HIV Agents, Down-Regulation, Flow Cytometry, Oceans and Seas, stromal cell-derived factor-1alpha, In Vitro, Human, Economics, genetics

020707
TuOrA1137