Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dendritic cells (DC) act as potent primary antigen-presenting cells in many immune responses and therefore may have a role in the initiation and perpetuation of the synovial inflammation in chronic inflammatory arthritis. To examine their function, it is important to isolate fresh DC from arthritic joints without aberrant activation. We have developed a technique using minimal cell manipulation to isolate DC from the synovial fluid of chronic arthritic patients. Using this method, DC were shown to be potent allostimulatory cells, with 63-90% of cells lacking lineage-specific markers (lin-), but positive for MHC class II molecules. Two morphologically distinct populations of these cells were identified in 10 out of 13 DC preparations. Both populations expressed CD40, intercellular adhesion molecule-1 (ICAM-1), ICAM-2, ICAM-3 and leucocyte function associated antigen-3 (LFA-3), but the predominant population, which was larger and more typical of cultured blood DC, had a higher density of these antigens compared with the minor population, which were smaller and morphologically similar to lymphocytes. Two new MoAbs which label activated human blood DC, HB15 (CD83) and CMRF-44, were tested. CD83 labelled very weakly or not at all, whereas CMRF-44 was positive on the larger cells only. Likewise, the costimulator molecule, B7/BB1 (CD80), was not detected on the surface of either synovial lin- cell population, reverse transcriptase polymerase chain reaction (RT-PCR) showed little or no CD80 mRNA, and no binding of the CTLA-4Ig fusion protein was found. These results suggest that synovial DC are not, despite the inflammatory environment, in a fully activated state.
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PMID:Dendritic cells in synovial fluid of chronic inflammatory arthritis lack CD80 surface expression. 753 11

Cultured Langerhans' cells (CLC) exhibit enhanced antigen-presenting function compared to freshly isolated LC (FLC), but they are commonly believed to be inefficient at processing intact proteins. In this study, FLC and CLC from normal, human immunodeficiency virus (HIV) seronegative volunteers were compared for their ability to present the HIV-1 envelope glycoprotein gp120 or reverse transcriptase (p66) antigens to autologous, specific CD4+ T cell lines. Epidermal cell suspensions enriched for LC were prepared from suction blister roofs. FLC stimulated T cells at lower antigen concentrations compared to unfractionated peripheral blood mononuclear cells (PBMC). CLC were more potent on a per cell basis than FLC, PBMC or adherent monocytes at presenting native gp120, native p66 or immunogenic peptides. CLC were also more efficient than FLC or PBMC in terms of the amount of antigen required for T-cell activation. Chloroquine and leupeptin inhibited presentation of intact p66, but not of an immunodominant peptide, by FLC or CLC, thus indicating that both cells utilize antigen-processing mechanisms that are based on intracellular acidification and protease activity. Incubation of CLC with monoclonal antibodies against HLA-DR, CD11b, CD18, CD50, CD54, CD58 or CD80, but not anti-major histocompatibility complex class I (MHC-I), inhibited antigen-specific T-cell proliferation to varying degrees. We conclude that human CLC retain the ability to process and present protein antigens potently to CD4+ T cells. Thus, CLC have the capacity to participate actively in the generation and maintenance of T-helper cell immunity to viral antigens during HIV-1 infection.
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PMID:Cultured human Langerhans' cells are superior to fresh cells at presenting native HIV-1 protein antigens to specific CD4+ T-cell lines. 869 96

Dendritic cells were identified in afferent lymph derived by lymphatic cannulation of cattle, stained with monoclonal antibody (mAb) to the bovine workshop cluster 6 (WC6) antigen, which is highly expressed on bovine afferent lymph veiled cells, and sorted with a fluorescence-activated cell sorter. These cells expressed major histocompatibility complex (MHC) class I and II and CD1b but not CD14. They bound human and murine CTLA4-immunoglobulin (CTLA4-Ig) fusion proteins indicating expression of CD80 and or CD86. Dendritic cells induced proliferative responses in allogeneic CD4+ and CD8+ cells sorted from blood but did not induce responses in purified allogeneic WC1+, gamma/delta T cells, which are CD2-, CD4-, CD8- and are the major gamma delta T-cell population in cattle blood, even when interleukin-2 (IL-2) was added to cultures. A WC1-, CD2+ gamma delta T-cell receptor (TCR)+ population predominates in cattle spleens and proliferation of a T-cell line with this phenotype was not induced by allogeneic dendritic cells, with or without added IL-2. The observations imply that the ligand for the gamma delta TCR expressed on the two populations is not present on allogeneic dendritic cells or that the costimulatory molecules expressed on dendritic cells that render them highly effective at stimulating MHC class I- and class II-restricted CD8+ and CD4+ T cells are not recognized by the WC1+ or WC1- gamma/delta T cells. Expression of CD28 by the four cell types was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR). Purified CD4+ and CD8+ cells both produced CD28 transcripts but neither purified WC1+ cells nor the WC1- gamma delta TCR+ cell line did so. The findings indicate that CD80 and or CD86 are involved in the stimulation of CD4+ and CD8+ alpha beta TCR+ T cells but not in the stimulation of either of the two gamma delta TCR+ populations.
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PMID:Afferent lymph veiled cells stimulate proliferative responses in allogeneic CD4+ and CD8+ T cells but not gamma delta TCR+ T cells. 888 57

We previously showed that approximately one-third of mouse primary microglial clones derived from individual precursor cells residing in normal brain constitutively present alloantigens (alloAgs) to naive CD8+ T cells (Moore et al.: J Neuroimmunol 41:203, 1992). To understand the basis for this alloAg presenting (alloAgP) activity, we developed a panel of microglial cell lines that were characterized by patterns of alloAgP activity similar to that of the primary clones. Flow cytometric analysis revealed that microglia with and without alloAgP activity expressed similar levels of major histocompatibility complex class I molecules; however, CD80 (B7-1) and CD86 (B7-2) expression was primarily restricted to the alloAgP- cell lines. Monoclonal antibody (Mab) to CD80 only partially blocked the proliferative response of allogeneic CD8+ T cells cocultured with the presenting cell lines, whereas Mab to CD86 completely inhibited the response, indicating a significant role for this molecule in T-cell activation. Using an immunoassay, recombinant mouse cytokines, cytokine-specific Mabs, and the reverse transcriptase-polymerase chain reaction to detect specific cytokine mRNAs, we found the synthesis of interleukin (IL)-1 alpha, IL-6, IL-12, and tumor necrosis factor-alpha (TNF-alpha) to be restricted to the alloAgP- cell lines. Costimulatory roles were then identified for these molecules. We conclude that the ability to present alloAg is a property of a subset of microglia that constitutively express CD86 and secrete costimulatory cytokines that promote the expansion of the alloAg-stimulated CD8+ T cells.
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PMID:Alloantigen presentation to naive CD8+ T cells by mouse microglia: evidence for a distinct phenotype based on expression of surface-associated and soluble costimulatory molecules. 891 75

The costimulatory signal through CD80 or CD86 to its counterreceptor CD28 or CTLA-4 on T cells has been shown to play an important role in the induction of T-cell-mediated immunity against tumors. In the present study, we examined the expression of CD80 and CD86 in the cell lines derived from human gastric, esophageal and colorectal carcinomas at the mRNA level, by means of a reverse transcriptase/polymerase chain reaction analysis and, for their surface expression, using a flow-cytometric analysis with monoclonal antibodies (mAb). The expression of mRNA for CD80 or CD86 was detected in all 18 cell lines tested, except for CD86 on one cell line. The cells from 13 (72%) or 12 (67%) of these cell lines expressed the surface CD80 or CD86 molecule, detected with the respective mAb. The surface expression of CD80 or CD86 was increased in four to five of the six cell lines tested after a culture with interferon gamma (IFN gamma). In addition, the up-regulation of CD80 or CD86 expression by IFN gamma was inhibited by interleukin-10 (IL-10). These results indicated that, in the cell lines derived from human gastrointestinal carcinoma, both the costimulatory molecules CD80 and CD86 were detectable in the majority of the cell lines examined at the mRNA and protein levels, and could be regulated with the cytokine IFN gamma or IL-10.
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PMID:The expression of costimulatory molecules CD80 and CD86 in human carcinoma cell lines: its regulation by interferon gamma and interleukin-10. 900 66

To understand the molecular basis of parasite-specific anergy in human lymphatic filariasis caused by the nematode Wuchereria bancrofti, parasite antigen-dependent cellular proliferation and cytokine gene expression were investigated. By reverse transcriptase polymerase chain reaction (RT-PCR), the levels of cytokine mRNA were determined in the peripheral blood mononuclear cells (PBMCs) of different clinical groups of filariasis patients. This includes individuals with circulating microfilariae (MF), patients with chronic lymphatic obstruction (CP), and exposed but uninfected individuals (EN). Those with CP exhibited both a Th2 and a Th1 parasite antigen-driven response. In PBMCs from those with MF, there was a marked downregulation of cellular response to parasite antigens, with lowered expression of Th1-specific cytokines (IFN-gamma and IL-2) and this was paralleled by increased IL-10 expression. The EN individuals had a purely Th1-type pattern with absence of IL-4 and IL-5 expression. Further, the mRNA expression of the costimulatory surface marker, CD80 (B7-1), was not associated with either disease status or IL-10 expression. There was a significant negative correlation between IL-10 mRNA expression and PBMC proliferation in the MF individuals, thus indicating the possible role of IL-10 in antigen-specific hyporesponsiveness.
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PMID:Elevated IL-10 mRNA expression and downregulation of Th1-type cytokines in microfilaraemic individuals with Wuchereria bancrofti infection. 907 9

Cervical carcinoma is strongly associated with human papillomavirus (HPV) type 16, and the transforming viral genes E6 and F7 are steadily expressed by the tumor cells. Therefore these viral oncogenes may be regarded as tumor-associated antigens. Our previous studies showed that cervical cancer cells after introduction of the CD80 gene activated allogeneic cytotoxic T lymphocytes (CTLs). In this study, we tested whether HPV 16+ cervical tumor cells (CaSki) expressing CD80 were able to activate CTLs recognizing HPV 16 E7 antigen. To this end, CD80+ CaSki cells (HLA-A*0201+) were used to stimulate peripheral blood T lymphocytes from HLA-A*0201+ healthy donors. We found that the activated T cells were able to lyse parental CaSki cells as well as Epstein-Barr virus-immortalized autologous B cells loaded with HLA-A*0201-restricted E7 peptides (amino acids 11-19, 82-90, 86-93). In contrast, no lysis was observed against target cells loaded with a control HIV-reverse transcriptase peptide (amino acid 476-484, HLA-A 0201-restricted). Our data, for the first time, provide evidence that CD80-expressing cervical cancer cells are able to activate tumor-specific CTLs using HPV 16 E7 as tumor-associated antigens.
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PMID:Cervical carcinoma cells transfected with the CD80 gene elicit a primary cytotoxic T lymphocyte response specific for HPV 16 E7 antigens. 940 8

We compared the immunological functions of interferon-gamma (IFN-gamma)-induced, classically activated macrophages (caM phi) and of interleukin-4 (IL-4)- and glucocorticoid-induced, alternatively activated macrophages (aaM phi) in a human co-culture system in vitro. Proliferation of peripheral blood leucocytes (PBL) or CD4+ T cells mediated by optimal doses of phytohaemagglutinin (PHA) or concanavalin A (Con A) was only marginally influenced by caM phi, but was strongly inhibited by aaM phi. The degree of lymphocyte proliferation sustained in the presence of caM phi was gradually reduced in a dose-dependent fashion by the addition of aaM phi. Flow cytometric analysis revealed that expression of costimulatory molecules such as CD11a, CD40, CD54, CD58, CD80 and CD86 did not vary significantly between caM phi and aaM phi and was low for CD58, CD80 and CD86. As shown by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, IL-10 was expressed in caM phi, aaM phi and control macrophages; the level of expression of IL-10 was slightly enhanced in aaM phi. Neither neutralizing anti-IL-10 antibodies, indomethacin nor NG-monomethyl-L-arginine (NMMLA) was able to reverse aaM phi-mediated inhibition of lymphocyte proliferation. Of several agents interfering with various second messenger pathways, cAMP and the Ca(2+)-ionophore A23187 inhibited differentiation of cultured human monocytes into phenotypically mature aaM phi expressing MS-1 high molecular weight protein (MS-1-HMWP) and RM 3/1 antigen, and prevented the suppressive action of aaM phi on lymphocyte proliferation. In conclusion, these results who that aaM phi actively inhibit mitogen-mediated proliferation of PBL and CD4+ T cells independently of the expression of costimulatory molecules and of IL-10, NO or prostaglandin synthesis, and that inhibition of phenotypic differentiation of aaM phi is paralleled by a lack of functional maturation. Thus, fully matured aaM phi may be functional in down-regulating CD4+ T-cell-mediated immune reactions by an as yet unknown mechanism.
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PMID:Alternatively activated macrophages actively inhibit proliferation of peripheral blood lymphocytes and CD4+ T cells in vitro. 949 89

CD43/leukosialin is a major sialoglycoprotein of the dendritic cell (DC) surface, which can regulate cell adhesion and has the potential to mediate cell activation signals. Monocyte-derived DC transiently incubated with the anti-CD43 mAb, MEM-59, or with F(ab')2 fragments, but not with monovalent Fab fragments or control IgG, 24 h later showed increased levels of membrane HLA-DR, CD54, CD40, CD80, CD86, and CD83. In parallel, CD43 cross-linking induced synthesis and release of IL-1beta, IL-6, TNF-alpha, IL-12, and IL-10. CD43 ligation inhibited the endocytic activity of DC, and enhanced the capacity of DC to stimulate T cell proliferation in the primary allogeneic and autologous MLR assay. In addition, anti-CD43-treated DC were less efficient at presenting native HIV-1 reverse transcriptase to a specific CD4+ T cell clone, whereas presentation of the reverse transcriptase 55-72 peptide to the same clone was increased. Finally, MEM-59 or its F(ab')2 fragments elicited a rise in intracellular free calcium and tyrosine phosphorylation of a 25-kDa protein in DC. The results thus indicate that CD43 cross-linking with specific ligands induces activation and functional maturation of DC.
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PMID:Cross-linking of membrane CD43 mediates dendritic cell maturation. 1035 44

Activated vascular endothelial cells (ECs) express major histocompatibility complex (MHC) class II molecules in vitro and in vivo in acute and chronic allograft rejection. However, human ECs may be limited in their ability to effectively activate CD4(+) T cells, because they do not express members of the B7 family (CD80 and CD86) of costimulatory molecules. In this study, we show that ECs promote the full activation of CD4(+) T cells via trans-costimulatory interactions. By reverse transcriptase polymerase chain reaction, Western blot, and FACS((R)) analysis, we could not detect the expression of CD80 and CD86 on activated ECs and found minimal expression on purified CD4(+) T cells. In contrast, both CD80 and CD86 were expressed in allogeneic CD4(+) T cell-EC cocultures. Expression of CD86 peaked at early times between 12 and 24 h after coculture, whereas CD80 was not expressed until 72 h. Addition of anti-CD86 but not anti-CD80 monoclonal antibodies to cocultures inhibited IL-2 production and the proliferation of CD4(+) T cells to allogeneic donor human umbilical vein ECs (HUVECs), as well as to skin and lung microvascular ECs. Furthermore, we found that interferon gamma-activated ECs but not untreated ECs induced mRNA and cell surface expression of CD80 and CD86 on CD4(+) T cells, and these T cells were functional to provide a trans-costimulatory signal to autologous CD4(+) T cells. Blockade of MHC class II and lymphocyte function-associated antigen 3 but not other EC cell surface molecules on IFN-gamma-activated ECs inhibited the induction of CD86 on CD4(+) T cells. Transmigration of purified populations of monocytes across EC monolayers similarly resulted in the induction of functional CD86, but also induced the de novo expression of the cytokines interleukin (IL)-1alpha and IL-12. In addition, EC-modified monocytes supported enhanced proliferation of allogeneic and autologous CD4(+) T cells. Taken together, these data define the ability of the endothelium to modify CD4(+) T cells and monocytes for trans-costimulatory events. This unique function of the endothelium in alloimmune T cell activation has functional consequences for the direct and the indirect pathways of allorecognition.
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PMID:Endothelial cells modify the costimulatory capacity of transmigrating leukocytes and promote CD28-mediated CD4(+) T cell alloactivation. 1044 26


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