Human follicular dendritic cells remain uninfected and capture human immunodeficiency virus type 1 through CD54-CD11a interaction

Abstract

It has been reported that human immunodeficiency virus type 1 (HIV-1) bound to follicular dendritic cells (FDCs) remains highly infectious to CD4(+) T cells even when it forms immune complexes with neutralizing antibody (HIV-1/IC). To elucidate the role of FDCs in HIV-1 transmission to CD4(+) T cells in lymph nodes, we have isolated and purified FDCs from human tonsils and examined whether the HIV-1/IC trapped on their surface is infectious to CD4(+) T cells. To our surprise, not the HIV-1/IC but the antibody-free HIV-1 on FDCs could be transmitted to CD4(+) T cells. Furthermore, in contrast to previous studies showing that FDCs are productively infected with HIV-1, the present study clearly demonstrated that FDCs were not the target cells for HIV-1 infection. FDCs could capture the viral particles on their surface; however, the binding of HIV-1 to FDCs was strongly inhibited by the presence of anti-CD54 (ICAM-1) monoclonal antibody (MAb) and anti-CD11a (LFA-1) MAb, suggesting that the adhesion molecules play an important role in the interaction between HIV-1 and FDCs.

Figures

FIG. 1

TEM for HIV-1/IC or HIV-1-exposed FDCs. An HIV-1/IC particle (arrow in panel A) was observed on the surface of FDC (×25,000). Twenty-eight viral particles were observed on the surface of 54 FDCs (51.9%). Similarly, an antibody-free HIV-1 particle (arrow in panel B) was captured on the top of a delicate cytoplasmic process of FDCs (×10,000; inset, ×75,000). Twenty-seven particles were observed on the surface of 55 FDCs (49.1%). Pleural virions (arrows in panel C) were often observed among the extracellular spaces of fine cytoplasmic processes of FDCs in isolated FDC-lymphocytes complex (FDC cluster) (×8,000). In contrast, such virions were scarcely identified on the surfaces of FDCs treated with a combination of anti-CD54 MAb and anti-CD11a MAb (panel D). Only one particle was identified on the 64 FDCs (1.6%). Desmosomal junctions, which are a reliable morphological marker of FDCs, were observed in panels B and D (arrowheads). These pictures are representative electron micrographs of some FDCs analyzed in this study.

FIG. 2

Inhibitory effects of anti-adhesion molecule MAbs on the entrapment and infectivity of HIV-1 in FDC cultures. FDCs were isolated and purified from human tonsils and exposed to HIV-1 at 4°C for 12 h in the absence (a) or in the presence of anti-CD54 (ICAM-1) MAb (b), anti-CD11a (LFA-1) MAb (c), anti-CD54 MAb plus anti-CD11a MAb (d), or anti-CD106 (VCAM-1) MAb (e). The cells were extensively washed and incubated at 37°C. After a 5-day incubation, FDCs were cocultured with activated CD4+ T cells in fresh culture medium for 4 days. The p24 antigen levels were determined by antigen capture ELISA and expressed as a percentage of the control culture (a). The mean values in each group are indicated by horizontal bars, and the statistical significance was analyzed by the t test.