The decreased proportion of blood dendritic cells correlated with virus replication and the lack of dendritic cells expressing CD11c are the first evidence of strong dendritic cell alterations in HIV-positive patients. Although the proportion of blood dendritic cells are in the normal range in treated HIV-positive patients with undetectable viral load, the CD11c alterations persist indicating that antiretroviral therapy might only partly correct the alterations of the circulating dendritic cells.
Degradation of chromosomal DNA into nucleosomesized fragments is one of the characteristics of apoptotic cell death. Here, we examined whether caspase-activated DNase (CAD) is responsible for the DNA fragmentation that occurs upon exposure to various apoptotic stimuli. When human Jurkat cells were exposed to etoposide, or UV or g radiation, a caspase-3-like protease was activated, and nuclear DNA was fragmented. Human TF-1 cells, which are dependent on granulocyte-macrophage colony-stimulating factor (GM ± CSF), also underwent apoptosis accompanied by the activation of caspase-3-like protease and DNA fragmentation, when cultured without the cytokine. Both Jurkat and TF-1 cells expressed two forms of ICAD, ICAD-L and ICAD-S, which were cleaved upon exposure to these apoptotic stimuli. Among eight di erent caspases examined, recombinant caspases 3 and 7 speci®cally cleaved ICAD synthesized in a cell-free system. An expression plasmid containing mouse ICAD-L mutated at the caspase-3-recognition sites was then introduced into Jurkat and TF-1 cells. When the transformants were induced to undergo apoptosis (by treatment with etoposide, UV or g radiation for Jurkat cells, or factor withdrawal for TF-1 cells) they did not show DNA fragmentation, although they still died as a result of these stimuli. These results indicated that CAD, released from ICAD by caspase activation, is involved in the nuclear DNA fragmentation induced by these apoptotic stimuli.
Expression of a mannoselfucose membrane lectin on human dendritic cellsDendritic cells (DC) are the most efficient antigen presenting cells for T lymphocytes. CDla' CD14-DC with high antigen-presenting capacities can now be obtained easily from adherent peripheral blood monocytes by culture in the presence of granulocyte/macrophage colony-stimulating factor and interleukin-4 (Sallusto et al., J . Exp. Med. 1994. 179: 1109). Human macrophages express a membrane lectin, or sugar-specific receptor, which specifically mediates the binding and endocytosis of mannose-and fucose-terminated glycoproteins and is involved in the phagocytosis of pathogens. Asimilar lectin activity was sought on cultured human DC using flow cytometry and confocal microscopy to detect binding and internalization of fluoresceinated neoglycoproteins [bovine serum albumin (BSA) substituted with sugar residues]. Several neoglycoproteins, especially a-L-fucosyl-, a-D-mannosyl-, N,N'-di-acetyl-P-chitobiosyl-and 0-Dglucosyl-BSA, were endocytosed by cultured human CDla' DC as well as by CDla-CD14-cells which were also obtained in the culture. Fuc-BSA and Man-BSA had the same number of binding sites (1.7 x 10h/cell) on CDla' DC, and bound with an affinity constant close to lo7 Vmol. Inhibition experiments indicated that these two neoglycoproteins bound to the same membrane lectin. CDla' and CDla-cells were both labeled by an antiserum specific for the human macrophage mannose receptor. The membrane lectin specific for mannose and fucose that is evidenced in these experiments on cultured DC may be similar to the macrophage membrane lectin or may share functional and structural properties with it. IntroductionDendritic cells (DC) are particularly efficient in presenting antigens to naive as well as to mature T lymphocytes [ 1-31. They initiate primary T cell responses in vivo and in vitro. They can stimulate an allogeneic mixed lymphocyte reaction with a much lower presenting celYeffector cell ratio than unseparated mononuclear cells, and they can present much lower concentrations of antigens than macrophages or nonspecific B lymphocytes [l]. DC are derived from human myeloid-lineage cells and express high levels of MHC class I and MHC class I1 molecules, CD40, CD80 (B7.1) and CD86 (B7.2) co-stimulatory molecules, several
Most monocyte-derived dendritic cells (DC) display CD1a, like Langerhans cells (LC) and some dermal DC, but their relationship with these skin DC remains unclear. To address this issue, we studied the expression of different antigens characteristic of skin DC and of monocyte/macrophages in CD1a ؉ and CD1a ؊ monocyte-derived DC. Their phenotype indicated that they may be related to dermal DC rather than to LC, i.e., they were all CD11b-positive, and 72% were Factor XIIIapositive, but they did not express E-cadherin nor VLA-6. It is interesting that CD1a ؉ and CD1a
Although the mouse spleen dendritic cell (DC) is perhaps the most intensively studied DC type, little has been published concerning its human equivalent. In this report, rare event flow cytometry and in situ immunofluorescence were used to study the surface phenotype and distribution of HLA-DR ؉ CD3 ؊ 14 ؊ 16 ؊ 19 ؊ human spleen DC. Spleens from organ donors with different clinical histories were used. Most (81% ؎ 9%; n ؍ 14) spleen DCs expressed high levels of the integrin CD11c. CD11c ؉ DCs were distributed in 3 distinct regions-the peri-arteriolar T-cell zones, the B-cell zones, and the marginal zone, where they formed a ring of cells surrounding the white pulp, just inside a ring of CD14 ؉ red pulp macrophages, apparently more regularly organized than the previously described marginating DC population in the mouse spleen. The Tcell zones contained CD86 ؉ DCs, among which a subpopulation expressed CD83. These mature/activated CD86 ؉ DCs represented a minority (12% ؎ 8%) of total spleen DCs in most organ donors: most spleen DCs are immature. In 3 of 18 (17%) donors, however, most (54%-81%) of spleen DCs were CD86 ؉ , suggesting that in vivo DC activation had occurred. In one donor, a radical shift in DC distribution from the marginal zone to the T-cell zones was also observed. This activation of spleen DCs in vivo was reminiscent of the effects of experimental microbial product injection in mice, and it seemed to correlate with bacterial infection or multiple trauma. (Blood. 2001;97:3470-3477)
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