Dendritic Cells In Lymphoid Tissues Research Articles

Blocking of the B7-CD28 pathway increases apoptosis induced in activated T cells by in vitro-generated CD95L (FasL) positive dendritic cells

D ENDRITIC cells (DC) that express high levels of MHC class II and costimu!atory molecules are the most potent antigen-presenting cells and the only population that can activate naive T cells. 1 Evidence has also accumulated, however, that DC can playa role in tolerance induction. Thus, thymic DC induce central tolerance to MHC antigens.: The ubiquitous presence of donor DC in long-surviving human and animal organ allograft recipients suggests that DC may hold the key to the induction of transplantation tolerance.3.4 We have reported that costimulatory molecule-deficient DC induce alloantigen-specific unresponsiveness in vitro,S and prolong allograft survival.°.7 The mechanisms by which tolerance can be induced by DC, however, remain unclear. A recent report indicates that CD8+ Fas-L + (CD95L +) mouse lymphoid tissue DC can induce apoptosis in activated T cells in vitro.s The present study was undertaken to evaluate the capacity of in vitro propagated DC to induce allogeneic T-cell apoptosis and to determine the possible regulatory roles of CD95 (Fas/Apo-I) ligand and B7 molecules expressed on DC.

The influence of granulocyte/macrophage colony‐stimulating factor on dendritic cell levels in mouse lymphoid organs

To ascertain whether the development of dendritic cells (DC) in mouse lymphoid organs is dependent on granulocyte/macrophage colony-stimulating factor (GM-CSF), we determined the number of DC in the thymus, spleen and lymph nodes of normal mice, of mice with the genes coding for GM-CSF or its receptor inactivated, and of transgenic mice with excessive levels of GM-CSE DC were extracted from the tissues and enriched prior to flow cytometric analysis. The total DC level and the incidence of DC expressing lymphoid-related markers (CD8(hi) CD11b(lo)) and myeloid-related markers (CD8(lo) CD11b(hi)) were monitored. Both in GM-CSF null mice, and GM-CSF receptor null mice, DC of all surface phenotypes were present in all lymphoid organs; only small decreases in DC levels were recorded, except for the lymph nodes of GM-CSF receptor null mice which showed a more pronounced (threefold) decrease in DC numbers. Since the GM-CSF receptor null mice lacked the beta chain common to the GM-CSF, interleukin (IL)-3 and IL-5 receptors, the development of DC in the absence of GM-CSF was not due to common beta chain mediated developmental signals elicited by IL-3 or IL-5. In GM-CSF transgenic mice, there was only a 50 % increase in DC numbers in thymus and spleen, paralleling an increase in overall cellularity, but a more pronounced (threefold) increase in DC numbers in lymph nodes. There was no evidence that GM-CSF had a selective effect on any particular DC subpopulation defined by CD8 or CD11b expression. We conclude that the development of most lymphoid tissue DC can proceed in the absence of GM-CSF, although this cytokine can produce some elevation of DC levels. It is not clear whether the enhancing effect of GM-CSF is direct or an indirect effect mediated by other cytokines.

Blocking of the B7-CD28 pathway increases the capacity of FasL+ (CD95L+) dendritic cells to kill alloactivated T cells.

Dendritic cells (DC) are antigen presenting cells of hemopoietic origin, uniquely well-equipped to activate naive T cells.1 Evidence also exists however, for DC tolerogenicity.2 During primary activation, mature T cells change from an activation-induced cell death (AICD) -resistant to an AICD-sensitive phenotype.3 The complete molecular basis for this transition remains to be determined, but CD95 (Fas/Apo-1) and CD95L (Fas ligand; FasL) appear to play an important role in the homeostatic regulation of T cell responses.4 It seems that CD95L can mediate opposite effects (T cell activation or apoptosis) depending on the state of activation of the responding T cells. Previously, we have shown that mouse bone marrow (BM)-derived DC progenitors deficient in expression of cell surface costimulatory molecules B7-1 (CD80) and B7-2 (CD86) are capable of inducing alloantigen-specific T cell hyporesponsiveness5 and prolonging allograft survival.6 Others have shown recently that a major subpopulation of freshly-isolated mouse lymphoid tissue DC is FasL+, and can induce apoptosis in allogeneic T cells.7 In the course of studies on DC propagated in vitro from mouse BM, we observed that these cells expressed Fas L. Our aim was to determine whether these cells could induce T cell apoptosis and whether costimulatory molecule expression could affect this activity.

P-Selectin Glycoprotein Ligand-1 Is Broadly Expressed in Cells of Myeloid, Lymphoid, and Dendritic Lineage and in Some Nonhematopoietic Cells

P-selectin glycoprotein ligand-1 (PSGL-1) is a muclin-like glycoportein ligand for P- and E-selectin on myeloid cells and a subset of lymphocytes. We used flow cytometry and immunohistochemistry to examine expression of PSGL-1 on minor leukocyte populations, differentiating hematopoletic cells, and nonhematopoietic tissues using two monoclonal antibodies to distinct protein epitopes on PSGL-1. In the bone marrow, PSGL-1 was expressed on myeloid cells from the myeloblast stage to the segmented neutrophil, but was not detected on erythroblasts or megakaryocytes. All types of circulating myeloid cells expressed PSGL-1, and PSGL-1 was retained after extravasation of myetoid cells into tissues. PSGL-1 was also expressed on circulating dendritic cells, monocyte-derived dendritic cells, dendritic cells in lymphoid tissues and epidermis, and follicular dendritic cells. All types of lymphoid cells examined expressed PSGK-1, including immature and mature thymocytes, naive and memory T cells, gamma/delta T cells, netural killer cells, B cells and CD34+ progenitor cells. However, PSGL-1 levels were substantially lower on tonsillar lymphocytes than on circulating lymphocytes, suggesting that PSGL-1 expression is down regulated during or after entry of lymphocytes into secondary lymphoid tissue. Although PSGL-1 antigen was detected primarily on hamatopoietic cells, it was also present on time epithelium of the fallopian tube. Furthermore, PSGL-1 antigen gen was detected sporadically on microvascular endothelium in some pathologic tissues. This suggests that PSGL-1 may have functions other than mediating leukocyte adhersion.

Processing and presentation of intact hen egg-white lysozyme by dendritic cells.

Dendritic cells in lymphoid tissues are of key importance as highly specialized antigen-presenting cells for the induction of T lymphocyte responses. Conflicting results have been published regarding antigen processing of intact proteins by dendritic cells. We now report that highly purified dendritic cells isolated from H-2k mouse spleens very efficiently generated immunogenic fragments of intact hen egg-white lysozyme (HEL) protein to present to an I-Ak-restricted T hybridoma cell line, specific for HEL peptide 46-61. Dendritic cells required 100 times less HEL protein than lipopolysaccharide-induced B cell blasts for effective presentation. Uptake of 125I-labeled HEL protein by dendritic cells and inhibition of presentation of HEL protein by chloroquine treatment was observed. This indicates an endocytotic process and the involvement of acidified compartments. Since the supernatant of dendritic cells, that were incubated with intact HEL protein, contained immunogenic fragments, further evidence for processing of HEL protein by dendritic cells was obtained. When HEL protein was covalently coupled to beads, dendritic cells were not able to ingest these beads, but could still process HEL protein for presentation. This suggests cell surface processing of HEL protein, although internalization of HEL protein released from the beads cannot be excluded. Taken together, these data show that H-2k dendritic cells are capable of processing and presenting intact HEL protein.

The Central Role of Follicular Dendritic Cells in Lymphoid Tissues

Publisher Summary This chapter discusses the role of follicular dendritic cells in lymphoid tissues. Characteristic features of primary and secondary lymphoid follicles are follicular dendritic cells (FDCs) that are not found in any other human organ. FDCs were first described as a nonlymphoid population of embryonic nonphagocytic reticulum cells. Other names for FDCs have been used in the past, for example, dendritic reticulum cells (DRCs), follicular dendritic reticulum cells, antigen-retaining reticular cells, follicular antigen-binding dendritic cells, and dendritic macrophages. FDCs are considered as having a passive role in the function of the germinal center. It is characterized as nonphagocytic cells that capture and retain complexes of antigen, antibodies, and C3 on their cell surface. By expressing antigen–antibody complexes and a large number of cell–cell and cellmatrix molecules, FDCs were shown to regulate normal B cell function. There is growing evidence that FDCs could be important constituents of the malignant counterpart of the germinal center. In addition, FDCs were demonstrated to be the target cells in human immunodeficiency virus (HIV)-related lymphadenopathy. These data can be integrated into a concept of FDCs as the key component of the germinal center microenvironment. FDCs demonstrate a unique antigen pattern by co-expressing myeloid and B cell markers.