Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06126 (CD1a)
 2,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe papular xanthomatosis that progressively developed in a patient with long-standing erythrodermic atopic dermatitis and normal lipid metabolism and without an associated systemic disease. Light microscopy showed a lobulated aggregate of sometimes foamy histiocytes. Ultrastructurally, these histiocytes contained lipid inclusions and lacked features of Langerhans or epithelioid cells. Other granulomatous skin diseases such as tuberculosis, sarcoidosis, or foreign body granuloma were excluded by histologic study, polarizing microscopic examination, electron microscopy, and microbiologic investigations. Nevertheless, these xanthomas showed an antigen expression pattern similar to that found in noninfectious granulomas (CD1a-, MS-1-, CD11c+, MRP-8/-14+, 25F9+, RM 3/1+/-, CD36(+), indicating that normolipemic papular xanthomatosis may be reactive process and should not be included among the true cutaneous non-Langerhans cell histiocytoses.
 ...
PMID:Normolipemic papular xanthomatosis in erythrodermic atopic dermatitis. 782 34

Since dendritic cells (DCs) are the most professional antigen-presenting cells, (Schuler et al., 1997), increasing interest in their use in clinical approaches has been observed. (Nestle et al., 1998; Murphy G. et al., 1996). We have developed an ex vivo standardized process for the generation of dendritic-like cells (MAC-DCs) from human blood circulating monocytes. Human monocytes can differentiate into very different functional cells according to the conditions of culture, media and cytokines used. In the present study, we demonstrate that both pure monocytes and mononuclear cells differentiate into DCs when they are grown in defined medium AIM-V in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) plus IL13 and in approved biocompatible non-adherent bags. Quality and functional controls of the immature DCs obtained rely on bacterial sterility, viability, morphology and recovery. The MAC-DCs also present an immature DC phenotype with a low expression of CD14 and CD64, and high expression of MHC-I, MHC-II and CD40. They also express B7 costimulatory molecules (CD80, CD86), CD83, and CD1a molecules. They induce strong allogenic T-cell proliferation (mixed lymphocyte reaction as well as proliferation of autologous memory T lymphocytes when incubated in the presence of recall antigens (tuberculosis, Candida albicans, and tetanus toxoid). They also show an increase in phagocytic uptake of yeast, tumour cells and debris. The global closed system which, under reproducible good medical practice (GMP) conditions, enables the production of dendritic cells of clinical quality, has been optimized ("Vac Cell Processor"). It contains all bags, connections, media, reagents, washing solutions, control antibodies, standard operating procedures, data management, traceability and help in the form of dedicated software.
 ...
PMID:Monocyte-derived dendritic cells: development of a cellular processor for clinical applications. 985 16

It is generally accepted that TCR alphabeta+ CD8+ T cells recognize immunogenic peptides bound to MHC-encoded class I molecules. This recognition is a major component of the cellular response mediating immune protection and recovery from viral infections and from certain intracellular bacterial infections. Here, we report two human CD8+ TCR alphabeta+ T cell lines specific for Mycobacterium tuberculosis Ags presented in the context of CD1a or CD1c Ag-presenting molecules. These T cells recognize lipid Ags and display cytotoxicity as well as strong Th cell type I cytokine responses. By extending presentation by the CD1 system to the major TCR alphabeta+ CD8+ T cell pool, this system gains wider applicability beyond the double negative subset of T cells previously shown to have this reactivity. This implies that previous assumptions about the role of CD8+ T cells in microbial immunity may require revision as the relative proportions of CD1-restricted and MHC class I-restricted CD8+ T cells are further defined.
 ...
PMID:CD1-restricted microbial lipid antigen-specific recognition found in the CD8+ alpha beta T cell pool. 988 8

Dendritic cells (DC) are powerful antigen presenting cells, which have the unique capacity to stimulate naive T cells. In spite of the well-known decline of T cell function in old age, little information is available on whether DC are also affected by the aging process. This is mainly due to problems with the isolation and purification of DC. Rapid progress in the characterization of DC has been made in recent years, as simple methods to generate large numbers of DC from precursors have been developed. It was the aim of the present study to compare monocyte derived DC from old and young healthy persons. The generation of DC from blood monocytes in response to GM-CSF and IL-4 treatment was similar in cells from young and old persons. The DC population thus obtained had a typical dendritic morphology and expressed DC surface markers, such as HLA class II, CD1a, CD11c, CD54, CD80 and CD86, but not CD14 for a period of up to three weeks in culture. DC from young and old persons produced IL-12 and TNF-alpha and responded equally well to maturation-inducing stimuli. DC maturation was stimulated by purified protein derivative (PPD) of Mycobacterium tuberculosis, whole inactivated influenza virus and by influenza split vaccine, but not by purified viral RNA. When tested for their antigen-presenting capacity, DC from young and old persons were capable of stimulating the proliferation and the cytokine production of T cells. It was of particular interest that CD45RA(+) as well as CD45RO(+) T cells from aged donors were unable to respond to stimulation with influenza proteins presented by monocytes, but were triggered to proliferate and to produce cytokines when antigen was presented by DC. The results demonstrate that DC from old persons (a) may still function as powerful antigen-presenting cells provided the right differentiation and maturation stimuli are present; (b) are capable of mobilizing residual capacity in senescent T cells and (c) may therefore represent a potent tool for immunotherapy and vaccines in old age.
 ...
PMID:Unimpaired dendritic cells can be derived from monocytes in old age and can mobilize residual function in senescent T cells. 1068 36

Glycolipid-specific, CD1a-, b- and c-dependent cytotoxic T cells have recently been shown to be involved in the host response against tuberculosis. These CD1 molecules 'sample' mycobacterial glycolipids from different intracellular sites in the infected cell. Additionally, upon microbial encounter, CD1d-dependent natural killer T cells promptly produce cytokines and perform regulatory activities. Here, we discuss the intracellular localization of CD1 molecules and mycobacterial lipids and the role of CD1-mediated T-cell responses in mycobacterial infections.
 ...
PMID:CD1 and CD1-restricted T cells in infections with intracellular bacteria. 1120 Dec 61

Sarcoidosis, a chronic granulomatous disease of unknown etiology, is treated with immune suppressive drugs such as corticosteroids. Sarcoidosis patients have been reported to benefit clinically from treatment with thalidomide. We administered thalidomide for 16 weeks to eight patients with chronic skin sarcoidosis and evaluated the drug's effects before and with treatment. After thalidomide treatment, all skin biopsies showed decreases in granuloma size and reduction in epidermal thickness. We also observed extensive T cell recruitment into the granulomas, the appearance of multinucleated giant cells, and increased numbers of dermal Langerhans cells (CD1a(+)) and mature dendritic cells (CD83(+) or DC-LAMP(+)). Plasma IL-12 levels increased and remained elevated during the treatment period. We noted increased HLA-DR expression on peripheral blood lymphocytes and a corresponding drop in the naive T cell marker CD45RA. Our data suggest that thalidomide treatment of sarcoidosis results in granuloma differentiation to a Th1-type cellular immune response usually associated with protective immunity to tuberculosis and tuberculoid leprosy.
 ...
PMID:Thalidomide induces granuloma differentiation in sarcoid skin lesions associated with disease improvement. 1189 Jul 9

Dendritic cells (DC) are potent APCs that sample Ags from the surrounding environment and present them to naive T cells using cell surface Ag-presenting molecules. The DC in both lymphoid and nonlymphoid tissues express high levels of CD1, a cell surface glycoprotein capable of presenting lipids and glycolipids to T cells. Distinct group 1 CD1 isoforms (CD1a, -b, -c) in man are known to traffic to different parts of the endocytic system where microbial Ags may be sampled. Guinea pigs are the only known rodent species that express the group 1 CD1 proteins. Therefore, we examined the expression and trafficking of guinea pig CD1 (gpCD1) isoforms on isolated DC. Confocal microscopy using mAbs specific for individual gpCD1 isoforms revealed differential trafficking of two distinct CD1b isoforms within DC. Colocalization of MHC class II was observed with the gpCD1b1 isoform, consistent with localization in the late endosomes of DC. In contrast, the gpCD1b3 isoform lacks an endosomal sorting motif and remains on the cell surface. Following incubation with Mycobacterium tuberculosis lipoarabinomannan, colocalization of endocytosed lipoarabinomannan with the gpCD1b1 isoform was observed but not with the gpCD1b3 isoform, which remained primarily on the cell surface. These data demonstrate that guinea pig DC express CD1 isoforms with unique trafficking patterns that recapitulate the patterns seen for human CD1 isoforms. This suggests evolutionary pressure for a conserved mechanism in mammals that allows CD1 to sample lipid Ags from various subcompartments of the endocytic system.
 ...
PMID:Conservation of CD1 intracellular trafficking patterns between mammalian species. 1247 Nov 29

Triggering receptor expressed on myeloid cells (TREM)-1 is a cell surface molecule expressed on neutrophils and monocytes implicated in the propagation of the inflammatory response. To further characterize the function of this molecule in different phases of the immune response, we examined TREM-1 in the context of host defense against microbial pathogens. In primary human monocytes TREM-1 activation did not trigger innate antimicrobial pathways directed against intracellular Mycobacterium tuberculosis, and only minimally improved phagocytosis. However, activation of TREM-1 on monocytes did drive robust production of proinflammatory chemokines such as macrophage inflammatory protein-1alpha and IL-8. Engagement of TREM-1 in combination with microbial ligands that activate Toll-like receptors also synergistically increased production of the proinflammatory cytokines TNF-alpha and GM-CSF, while inhibiting production of IL-10, an anti-inflammatory cytokine. Expression of TREM-1 was up-regulated in response to TLR activation, an effect further enhanced by GM-CSF and TNF-alpha but inhibited by IL-10. Functionally, primary monocytes differentiated into immature dendritic cells following activation through TREM-1, evidenced by higher expression of CD1a, CD86, and MHC class II molecules. These cells had an improved ability to elicit T cell proliferation and production of IFN-gamma. Our data suggest that activation of TREM-1 on monocytes participates during the early-induced and adaptive immune responses involved in host defense against microbial challenges.
 ...
PMID:A role for triggering receptor expressed on myeloid cells-1 in host defense during the early-induced and adaptive phases of the immune response. 1264 48

Unlike major histocompatibility proteins, which bind peptides, CD1 proteins display lipid antigens to T cells. Here, we report that CD1a presents a family of previously unknown lipopeptides from Mycobacterium tuberculosis, named didehydroxymycobactins because of their structural relation to mycobactin siderophores. T cell activation was mediated by the alphabeta T cell receptors and was specific for structure of the acyl and peptidic components of these antigens. These studies identify a means of intracellular pathogen detection and identify lipopeptides as a biochemical class of antigens for T cells, which, like conventional peptides, have a potential for marked structural diversity.
 ...
PMID:T cell activation by lipopeptide antigens. 1473 49

Human monocytes can differentiate into dendritic cells (DCs) according to the nature of environmental signals. We tested here whether the infection with the live tuberculosis vaccine bacillus Calmette-Guerin (BCG), which is known to be limited in preventing pulmonary tuberculosis, modulates monocyte and DC differentiation. We found that monocytes infected with BCG differentiate into CD1a- DCs (BCG-DCs) in the presence of granulocyte macrophage-colony stimulating factor and interleukin (IL)-4 and acquired a mature phenotype in the absence of maturation stimuli. In addition, BCG-DCs produced proinflammatory cytokines (tumor necrosis factor alpha, IL-1beta, IL-6) and IL-10 but not IL-12. BCG-DCs were able to stimulate allogeneic T lymphocytes to a similar degree as DCs generated in the absence of infection. However, BCG-DCs induced IL-4 production when cocultured with human cord-blood mononuclear cells. The induction of IL-4 production by DCs generated by BCG-infected monocytes could explain the failure of the BCG vaccine to prevent pulmonary tuberculosis.
 ...
PMID:Dendritic cells derived from BCG-infected precursors induce Th2-like immune response. 1524 Jul 55


1 2 3 4 Next >>