Generation of gut-homing IgA-secreting B cells by intestinal dendritic cells

Normal intestinal mucosa contains abundant immunoglobulin A (IgA)-secreting cells, which are generated from B cells in gut-associated lymphoid tissues (GALT). We show that dendritic cells (DC) from GALT induce T cell-independent expression of IgA and gut-homing receptors on B cells. GALT-DC-derived retinoic acid (RA) alone conferred gut tropism but could not promote IgA secretion. However, RA potently synergized with GALT-DC-derived interleukin-6 (IL-6) or IL-5 to induce IgA secretion. Consequently, mice deficient in the RA precursor vitamin A lacked IgA-secreting cells in the small intestine. Thus, GALT-DC shape mucosal immunity by modulating B cell migration and effector activity through synergistically acting mediators.     

TLR11 activation of dendritic cells by a protozoan profilin-like protein

Mammalian Toll-like receptors (TLRs) play an important role in the innate recognition of pathogens by dendritic cells (DCs). Although TLRs are clearly involved in the detection of bacteria and viruses, relatively little is known about their function in the innate response to eukaryotic microorganisms. Here we identify a profilin-like molecule from the protozoan parasite Toxoplasma gondii that generates a potent interleukin-12 (IL-12) response in murine DCs that is dependent on myeloid differentiation factor 88. T. gondii profilin activates DCs through TLR11 and is the first chemically defined ligand for this TLR. Moreover, TLR11 is required in vivo for parasite-induced IL-12 production and optimal resistance to infection, thereby establishing a role for the receptor in host recognition of protozoan pathogens.     

Toll-like receptor 4-dependent activation of dendritic cells by beta-defensin 2

beta-Defensins are small antimicrobial peptides of the innate immune system produced in response to microbial infection of mucosal tissue and skin. We demonstrate that murine beta-defensin 2 (mDF2beta) acts directly on immature dendritic cells as an endogenous ligand for Toll-like receptor 4 (TLR-4), inducing up-regulation of costimulatory molecules and dendritic cell maturation. These events, in turn, trigger robust, type 1 polarized adaptive immune responses in vivo, suggesting that mDF2beta may play an important role in immunosurveillance against pathogens and, possibly, self antigens or tumor antigens.     

Maintenance of serological memory by polyclonal activation of human memory B cells

Production of antibodies can last for a lifetime, through mechanisms that remain poorly understood. Here, we show that human memory B lymphocytes proliferate and differentiate into plasma cells in response to polyclonal stimuli, such as bystander T cell help and CpG DNA. Furthermore, plasma cells secreting antibodies to recall antigens are produced in vivo at levels proportional to the frequency of specific memory B cells, even several years after antigenic stimulation. Although antigen boosting leads to a transient increase in specific antibody levels, ongoing polyclonal activation of memory B cells offers a means to maintain serological memory for a human lifetime.     

Transmigration of lymph nodes by tumor cells

When either V2, Brown-Pearce, or Walker tumor cells were perfused at low pressure into the afferent lymphatic of popliteal lymph nodes or were injected into the foot pads of rabbits, they rapidly appeared in lymph draining from the node. This finding indicates that lymph nodes are not the effective barrier to dissemination of tumor cells they had previously been assumed to be.     

Autophagy-dependent viral recognition by plasmacytoid dendritic cells

Plasmacytoid dendritic cells (pDCs) detect viruses in the acidified endosomes by means of Toll-like receptors (TLRs). Yet, pDC responses to certain single-stranded RNA (ssRNA) viruses occur only after live viral infection. We present evidence here that the recognition of such viruses by TLR7 requires transport of cytosolic viral replication intermediates into the lysosome by the process of autophagy. In addition, autophagy was found to be required for the production of interferon-alpha by pDCs. These results support a key role for autophagy in mediating ssRNA virus detection and interferon-alpha secretion by pDCs and suggest that cytosolic replication intermediates of viruses serve as pathogen signatures recognized by TLR7.     

Protein-specific helper T-lymphocyte formation initiated by dendritic cells

Antibody responses to hapten-polypeptide conjugates require peptide-specific helper T cells. The latter can be primed in tissue culture by providing small numbers of dendritic cells. Primed, irradiated helper T cells then induce B-cell growth and differentiation in the apparent absence of dendritic cells. Both stages of the antibody response--the induction of helper T lymphoblasts by dendritic cells and the delivery of help from T to B cell--occur in discrete cell aggregates that can be isolated by velocity sedimentation. If helper T blasts revert to smaller "memory" lymphocytes, dendritic cells again are needed to initiate the antibody response.     

Distribution of S-100 positive dendritic cells in bovine pharynx, tonsils, and retropharyngeal lymph nodes

Dendritic cells (DCs) are professional antigen-presenting cells. However, the distribution of bovine DCs in the pharynx, tonsil, and retropharyngeal lymph nodes has not yet been documented. To address this issue, immunohistochemistry was conducted using S-100 protein as a marker for DCs. It was observed that S-100 positive Langerhans cells (LCs) were primarily found in the basal layer of the pharyngeal epithelium. Some DCs were found in the outer layer of the epithelium and their dendrites extended out towards the epithelial surface. In the tonsil, S-100 positive DCs were found either in follicular germinal centers or in the T-cell areas. It is worth noting that the S-100 positive DCs were not only distributed in the cortex, but also in the medulla of bovine retropharyngeal lymph nodes. The distribution patterns of bovine DCs in the pharynx, tonsil, and retropharyngeal lymph nodes have an important implication for our understanding of the interaction between pathogens and host.     

Immunologic tolerance: role of the regional lymph node

Dansyl chloride, a skin setnsitizer when injected in complete Freund's adjuvant, induced marked tolerance and no sensitization when applied to the intact skin of guinea pigs. Application of this chemical to alymphatic skin islands failed to induce tolerance or sensitization. Lymnphatic connections between skin and regional lymph nodes were essential for the developmnent of ismmunologic toleance.     

The spread of Ras activity triggered by activation of a single dendritic spine

In neurons, individual dendritic spines isolate N-methyl-d-aspartate (NMDA) receptor-mediated calcium ion (Ca2+) accumulations from the dendrite and other spines. However, the extent to which spines compartmentalize signaling events downstream of Ca2+ influx is not known. We combined two-photon fluorescence lifetime imaging with two-photon glutamate uncaging to image the activity of the small guanosine triphosphatase Ras after NMDA receptor activation at individual spines. Induction of long-term potentiation (LTP) triggered robust Ca2+-dependent Ras activation in single spines that decayed in approximately 5 minutes. Ras activity spread over approximately 10 micrometers of dendrite and invaded neighboring spines by diffusion. The spread of Ras-dependent signaling was necessary for the local regulation of the threshold for LTP induction. Thus, Ca2+-dependent synaptic signals can spread to couple multiple synapses on short stretches of dendrite.     

Induction of protective IgA by intestinal dendritic cells carrying commensal bacteria

The enormous number of commensal bacteria in the lower intestine of vertebrates share abundant molecular patterns used for innate immune recognition of pathogenic bacteria. We show that, even though commensals are rapidly killed by macrophages, intestinal dendritic cells (DCs) can retain small numbers of live commensals for several days. This allows DCs to selectively induce IgA, which helps protect against mucosal penetration by commensals. The commensal-loaded DCs are restricted to the mucosal immune compartment by the mesenteric lymph nodes, which ensures that immune responses to commensal bacteria are induced locally, without potentially damaging systemic immune responses.     

Epidermal viral immunity induced by CD8alpha+ dendritic cells but not by Langerhans cells

The classical paradigm for dendritic cell function derives from the study of Langerhans cells, which predominate within skin epidermis. After an encounter with foreign agents, Langerhans cells are thought to migrate to draining lymph nodes, where they initiate T cell priming. Contrary to this, we show here that infection of murine epidermis by herpes simplex virus did not result in the priming of virus-specific cytotoxic T lymphocytes by Langerhans cells. Rather, the priming response required a distinct CD8alpha+ dendritic cell subset. Thus, the traditional view of Langerhans cells in epidermal immunity needs to be revisited to accommodate a requirement for other dendritic cells in this response.     

Chemokine Up-regulation and activated T cell attraction by maturing dendritic cells

Langerhans' cells migrating from contact-sensitized skin were found to up-regulate expression of macrophage-derived chemokine (MDC) during maturation into lymph node dendritic cells (DCs). Na?ve T cells did not migrate toward MDC, but antigen-specific T cells rapidly acquired MDC responsiveness in vivo after a subcutaneous injection of antigen. In chemotaxis assays, maturing DCs attracted activated T cells more strongly than na?ve T cells. These studies identified chemokine up-regulation as part of the Langerhans' cell maturation program to immunogenic T cell-zone DC. Preferential recruitment of activated T cells may be a mechanism used by maturing DCs to promote encounters with antigen-specific T cells.     

Two-photon imaging of lymphocyte motility and antigen response in intact lymph node

Lymphocyte motility is vital for trafficking within lymphoid organs and for initiating contact with antigen-presenting cells. Visualization of these processes has previously been limited to in vitro systems. We describe the use of two-photon laser microscopy to image the dynamic behavior of individual living lymphocytes deep within intact lymph nodes. In their native environment, T cells achieved peak velocities of more than 25 micrometers per minute, displaying a motility coefficient that is five to six times that of B cells. Antigenic challenge changed T cell trajectories from random walks to "swarms" and stable clusters. Real-time two-photon imaging reveals lymphocyte behaviors that are fundamental to the initiation of the immune response.     

细胞角蛋白免疫组化染色对胃癌淋巴结转移的诊断意义

目的 探讨细胞角蛋白(CK)免疫组化染色在判断胃癌淋巴结转移中的作用.方法 采用常规HE染色、CK免疫组化染色检测51例胃癌根治术患者的淋巴结转移情况.结果 51例胃癌中,HE、CK免疫组化染色发现淋巴结转移检出率分别为58.8%、80.3%;在送检的848个淋巴结中,HE、CK免疫组化染色显示淋巴结转移率分别为12....     

Subacute sclerosing panencephalitis: isolation of suppressed measles virus from lymph node biopsies

Measles virus was isolated in mixed cultures of lymph node cells and HeLa cells. The agent was isolated by cocultivation from biopsy specimens of two of five patients with subacute sclerosing panencephalitis. The virus was identified by hemagglutination-inhibition, immunofluorescent, and neutralization tests. Biopsies from controls did not show evidence of measles virus.     

Adenyl cyclase of cultured mammalian cells: activation by catecholamines

Chang's liver cells and 3T6 mouse embryo fibroblasts contain high amounts of catecholamine-sensitive adenyl cyclase, whereas HeLa cells contain relatively low amounts of activity. Both epinephrine and fluoride ion stimulate activity of each cell line. In contrast to normal liver, Chang's liver cells show greater response to epinephrine and no detectable stimulation by glucagon.     

彩色多普勒超声对乳腺癌腋窝淋巴结转移的诊断价值

目的:评价彩色多普勒超声与临床触诊诊断乳腺癌腋窝淋巴结转移的灵敏度、特异度和准确度性。方法:应用双盲法对53例(55侧)行乳腺癌根治术患者的术前触诊、超声检查及术后病理检查进行对比分析。结果:55侧中,病理证实41侧有淋巴结转移,临床触诊和超声检出侧分别为35侧和39侧,触诊的灵敏度、特异度、诊断符合率分别为68.3%、50.0%、63.6%,超声则分别为87.8%、78.6%、85.5%,两组间的灵敏度及诊断符合率差异有统计学意义(P<0.05或<0.01),特异度则差异无统计学意义(P>0.05)。结论:超声检查腋窝淋巴结的灵敏度及诊断符合率均高于触诊,可作为诊断淋巴结转移的常规检查项目。     

Suppression of antitumor immunity by stromal cells expressing fibroblast activation protein-alpha

The stromal microenvironment of tumors, which is a mixture of hematopoietic and mesenchymal cells, suppresses immune control of tumor growth. A stromal cell type that was first identified in human cancers expresses fibroblast activation protein-α (FAP). We created a transgenic mouse in which FAP-expressing cells can be ablated. Depletion of FAP-expressing cells, which made up only 2% of all tumor cells in established Lewis lung carcinomas, caused rapid hypoxic necrosis of both cancer and stromal cells in immunogenic tumors by a process involving interferon-γ and tumor necrosis factor-α. Depleting FAP-expressing cells in a subcutaneous model of pancreatic ductal adenocarcinoma also permitted immunological control of growth. Therefore, FAP-expressing cells are a nonredundant, immune-suppressive component of the tumor microenvironment.