In all parts of epidermis, but more in the upper
spinosum layer, are dendritic cells described in 1868. These cells have a
dark
nucleus and pale, or clear cytoplasm. The dendritic or stellate form is
revealed by gold impregnation stains. The cell has no desmosomes
attaching it
to neighboring cells, no tonofilament bundles and no melanosomes.
However, it
doe contain smooth vesicles, multivesicular bodies and lysosomes, but most
characteristic is the Birbeck granules. These are
membrane-bound, rod
shaped, 15-50nm long, 4nm wide, with central linear density and faint
striations radiating from the linear density to the limiting membrane
(function
unknown). Also called Langerhans granules and vermiform granules. These
cells
participate in the cutaneous immune response and migrate from skin to
lymph
nodes. They possess surface receptors common to macrophages (receptors for
immunoglobulin Fc and complement C3) and function as antigen presenting
cells
to T or B lymphocytes. Langerhans cell serves to fix and process
cutaneous
antigens.Photo (upper left) from Siena et al. (see below).
Above description of Langerhans cells courtesy of:
R. Funnell (FUNNELL@MEDCOR.MCGILL.CA)
Siena S, Di Nicola M, Bregni M, Mortarini R, Anichini A, Lombardi L, Ravagnani F, Parmiani G,
Gianni AM. (1995). MASSIVE EX-VIVO GENERATION OF FUNCTIONAL DENDRITIC CELLS FROM MOBILIZED CD34(+) BLOOD PROGENITORS FOR ANTICANCER
THERAPY.
Exper. Hematol. 23(14), DEC 1995, pp. 1463-1471.
This method uses a cocktail of cytokines (GM-CSF, tumor necrosis factor (TNF), and flt3 ligand) to grow out adherent, "professional" antigen-presenting cells (APCs) in culture. These cells are reminiscent of dendritic cells, such as the Langerhans cell, a species of dendritic cell resident in skin.
Mature dendritic cells, a form found in tonsils, adenoids, and in lymph nodes are positive for CD1a, a "cluster of differentiation" (CD) antigen, positive for the cytosolic protein S100, and positive for the actin-bundle protein p55.
Human Dendritic Langerhans Cells Generated In Vitro from CD34+ Progenitors Can Prime Naive CD4+ T Cells and Process Soluble Antigen
Christophe Caux, Catherine Massacrier, Colette Dezutter-Dambuyant, Béatrice Vanbervliet, Christelle Jacquet, Daniel Schmitt, Jacques Banchereau
Transcriptional activation of the human immunodeficiency virus type 1
(HIV) gene expression in response to cellular factors represents an
important step in the process of viral infection. In the HIV LTR, several
regulatory motifs have been identified which are bound by cellular
proteins. For example a cooperative interaction between NF-
B and Sp1 has
been demonstrated for the efficient stimulation of HIV-1 transcription.
HIV-1 replicates in cultured T cells that have been stimulated by antigens
or mitogens; and HIV-1 replication in activated T lymphocytes has been
attributed to activation of NF-B. However
antigen activation may not be
essential for HIV-1 replication in patients. Viral replication can take
place in mixture of nonactivated T cells and skin dendritic cells. Active
virus replication is confined to HIV-1 induced, heterologous syncytia in
which dendritic cells and T cells fuse with one another. We have shown
that
the formation of these dendritic cell-T cell syncytia brings together
NF-B
via the dendritic cells with SP1 via the nonactivated T cell. This
phenomenon may contribute to chronic viral replication in situ. Current
studies focus on the characterization of other cellular factors involved
in
virus replication.
Taken from
http://www.rockefeller.edu/sep/steinman2.html#Granelli-Piperno
Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, NY 10021, USA.
Productive infection of T cells with human immunodeficiency virus 1 (HIV-1) typically requires that the T cells be stimulated with antigens or mitogens. This requirement has been attributed to the activation of the transcription factor NF-kappa B, which synergizes with the constitutive transcription factor Sp1 to drive the HIV-1 promoter. Recently, we have found that vigorous replication of HIV-1 takes place in nonactivated memory T cells after syncytium formation with dendritic cells (DCs). These syncytia lack activated cells as determined by an absence of staining for Ki-67 cell cycle antigen. The expression and activity of NF-kappa B and Sp1 were, therefore, analyzed in isolated T cells and DCs from humans and mice. We have used immunolabeling, Western blot analysis, and electrophoretic mobility shift and supershift assays. T cells lack active NF-kappa B but express Sp1 as expected. DCs express high levels of all known NF-kappa B and Rel proteins, with activity residing primarily within RelB, p50, and p65. However, DCs lack Sp1, which may explain the failure of HIV-1 to replicate in purified DCs. Coexpression of NF-kappa B and Sp1 occurs in the heterologous DC-T-cell syncytia that are induced by HIV-1. Therefore, HIV-1-induced cell fusion brings together factors that upregulate virus transcription. Since DCs and memory T cells frequently traffic together in situ, these unusual heterologous syncytia could develop in infected individuals and lead to chronic HIV-1 replication without ostensible immune stimulation.
Dendritic cells (DC) are the principle APC involved in primary immune responses; their major function is to obtain Ag in tissues, migrate to lymphoid organs, and activate T cells. DC are also the first immune cells to arrive at sites of inflammation on mucous membranes, the major site of sexual transmission of HIV. We have demonstrated previously that three populations of cells that can develop a dendritic morphology are present in peripheral blood. Two of these populations can express CD83, a marker of DC, and appear to be at different stages of maturation: 1) a precursor population and 2) a mature immunostimulatory DC. Precursor-derived DC express high levels of CD86 (B7-2) and HLA-DR but no CD80 (B7-1), whereas mature DC have high levels of expression of all three markers. Mature DC in peripheral blood bind HIV to their surface and induce infection when added to autologous CD4+ T cells in the absence of added stimuli, such as mitogens. These mature DC, when isolated directly from peripheral blood, appear to be conjugated to T cells, and these conjugates are infected easily and productively with HIV. These findings suggest a role for DC in early HIV infection in which they bind virus and interact with T cells locally or after migrating to a lymphoid organ, thus establishing a productive infection. Furthermore, they likely play a role in the propagation of HIV infection by activating T cells in the presence of HIV, which leads to viral replication and immune cell destruction.