Tumor formation involves the accumulation of a series of genetic alterations that are required for malignant growth. In most malignancies, genetic changes can be observed at the chromosomal level as losses or gains of whole or large portions of chromosomes. Here we provide evidence that tumor DNA may be horizontally transferred by the uptake of apoptotic bodies. Phagocytosis of apoptotic bodies derived from H-ras V12 -and human c-myc-transfected rat fibroblasts resulted in loss of contact inhibition in vitro and a tumorigenic phenotype in vivo. Fluorescence in situ hybridization analysis revealed the presence of rat chromosomes or of rat and mouse fusion chromosomes in the nuclei of the recipient murine cells. The transferred DNA was propagated, provided that the transferred DNA conferred a selective advantage to the cell and that the phagocytotic host cell was p53-negative. These results suggest that lateral transfer of DNA between eukaryotic cells may result in aneuploidy and the accumulation of genetic changes that are necessary for tumor formation.

Human immunodeficiency virus type 1 (HIV-1) infection of dendritic cells (DCs

Dendritic cells (DCs) are antigen-presenting cells with the capacity to prime naive T cells for efficient cellular responses against pathogens such as HIV-1. DCs are also susceptible to HIV-1 infection, which may impair their ability to induce immunity. Here, we examined the ability of HIV-1-infected, in vitro-derived DCs to respond to CD40 ligand (CD40L) stimulation with the aim to study events during early HIV-1 infection. HIV-1 BaL -infected p24 ؉ DCs were detected after only 3 days of exposure to highly concentrated virus. We show that HIV-1-infected DCs upregulated costimulatory molecules, but were skewed in their production of effector cytokines in response to CD40L stimulation. CD40L stimulation induced significant secretion of tumor necrosis factor ␣ (TNF␣) and interleukin 12 (IL-12) p70 from both HIV-1-exposed and unexposed DCs. Intracellular stainings of HIV-1-exposed DCs revealed that TNF␣ could be detected in both the p24 ؊ and p24 ؉ DCs, but IL-12 p70 could be found only in the p24 ؊ DCs. Thus, although p24 ؉ DCs showed a mature phenotype similar to p24 ؊ DCs after CD40L stimulation, they appeared to have an impaired cytokine profile. These observations suggest that HIV-1 infection disables DC function, a phenomenon that may be relevant for optimal induction of HIV-1-specific immune responses.