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Session 25 Oral Abstract Session Immunology Session Time: Wednesday, 10 am - 12:30 pm Room 6C

12:00   109. Constitutive and Induced Expression of DC-SIGN on Dendritic Cell and Macrophage Subpopulations in Situ and in Vitro E. J. Soilleux1, L. S. Morris1, G. Leslie2, J. Chehimi3, Q. Luo3, E. Levroney4, J. Trowsdale1 , L. J. Montaner3, R. W. Doms2, D. Weissman2, N. Coleman1, B. Lee*4, and 5 1Univ. of Cambridge, UK; 2Univ. of Pennsylvania, Philadelphia; 3Wistar Inst., Philadelphia, PA; 4Univ. of California, Los Angeles Sch. of Med.; and 5 Univ. of California, Los Angeles AIDS Inst. Background: DC-SIGN is a C-type lectin highly expressed on the surface of immature dendritic cells (DCs) that mediates efficient infection of T cells in trans by its ability to bind HIV-1, HIV-2, and SIV. In addition, the ability of DC-SIGN to bind adhesion molecules on surfaces of naïve T cells and endothelium also suggests its involvement in T-cell activation and DC trafficking. Methods: To gain further insights into the range of expression and potential functions of DC-SIGN, we performed a detailed immunohistochemical analysis of DC-SIGN expression in adult and fetal tissues, and also analyzed its regulated expression on cultured dendritic cells and macrophages. Triple-labelled confocal microscopy was used to determine whether DC-SIGN+ cells had a DC1 or a DC2 dendritic cell phenotype. Results: Firstly, we report that DC-SIGN expression is restricted to subsets of immature dendritic cells in tissues, and on specialized macrophages in the placenta and lung. There were no overt differences between DC-SIGN expression in adult and fetal tissues except that DC-SIGN expression in alveolar macrophages was only present after birth. Similarly, in tissues, DC-SIGN was observed primarily on immature (CD83-negative) dendritic cells. Secondly, since recent data have shown that plasmacytoid (DC2) dendritic cells are more permissive for HIV infection than myeloid dendritic cells, we sought to determine the phenotype of DC-SIGN-expressing cells, using a combination of these markers. In the peripheral blood, we found expression of DC-SIGN on a small subset of BDCA-2+ plasmacytoid dendritic cell precursors (pDC2), concordant with our finding of large numbers of DC-SIGN positive cells in allergic nasal polyps (previously shown to be infiltrated by DC2). Triple-labelled confocal microscopy indicated that DC-SIGN co-localized with BDCA-2 and CD123 on dendritic cells in nasal polyp tissue. Consistent with this finding is our observation that DC-SIGN can be upregulated on monocyte-derived macrophages upon exposure to the Th2 cytokine, IL-13. Conclusions: In summary, our data demonstrate the relevant populations of DC and macrophages that express DC-SIGN in vivo where it may impact upon the efficiency of virus infection and indicate that DC-SIGN expression may be involved in the Th2 axis of immunity.

©2002 9th Conference on Retroviruses and Opportunistic Infections