Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The object of the present investigation was to extend fundamental understanding of the composition, function and origin of bronchoalveolar lavage (BAL) cells, and to reduce the considerable gaps in our existing knowledge. BAL cells from the B10.D2 mouse were identified by morphological, enzyme cytochemical and immunocytochemical methods and a further functional characterisation of macrophages was undertaken in vitro using latex phagocytosis. The possible bone marrow origin of BAL cells was investigated with a radiation chimera. The bone marrow from H2k-positive F1 mice (B10.BR x B10.D2) was transplanted into the irradiated H2k-negative parent animals. At various time intervals after transplantation, BAL cells were tested immunocytochemically for the presence of H2k-positive cells. The principal finding was that BAL cells are functionally heterogeneous. It was possible by morphological, enzyme cytochemical and immunocytochemical techniques to subdivide the total BAL cell count into 89% macrophages, 8.5% lymphocytes and 2.5% granulocytes. Only 14.3% of the macrophages expressed the corresponding epitope, and this small population could be further subdivided immunocytochemically into mature and immature (7:1) macrophages. The ability to phagocytose, which is typical of active macrophages, could be induced in vitro in only one-third of all BAL macrophages. Three-quarters of the macrophages carried the H2d antigen and 9.5% of the BAL cells were natural killer cells showing a macrophage phenotype. Subdivision of the lymphocytes showed a significant majority of T-cells (75%) to B-cells (20%), and 5% Asialo GM1-positive cells. The CD4/CD8 ratio amounted to 1.3:1 and 38% of the lymphocytes expressed on the surface the H2d antigen.(ABSTRACT TRUNCATED AT 250 WORDS)
Virchows Arch B Cell Pathol Incl Mol Pathol 1993
PMID:Function and "homing" of the lung macrophages. I. Evidence of functional heterogeneity of mobile cells of the murine lung parenchyma in the bronchoalveolar lavage (BAL). 824 78

The CD4 protein plays a critical role in the development and function of the immune system. To gain more insight into the mechanism of expression of the human CD4 gene, we cloned 42.2 kbp of genomic sequences comprising the CD4 gene and its surrounding sequences. Studies with transgenic mice revealed that a 12.6-kbp fragment of the human CD4 gene (comprising 2.6 kbp of 5' sequences upstream of the transcription initiation site, the first two exons and introns, and part of exon 3) contains the sequences required to support the appropriate expression in murine mature CD4+ CD8- T cells and macrophages but not in immature double-positive CD4+ CD8+ T cells. Expression in CD4+ CD8+ T cells was found to require additional regulatory elements present in a T-cell enhancer fragment recently identified for the murine CD4 gene (S. Sawada and D. R. Littman, Mol. Cell. Biol. 11:5506-5515, 1991). These results suggest that expression of CD4 in mature and immature T-cell subsets may be controlled by distinct and independent regulatory elements. Alternatively, specific regulatory elements may control the expression of CD4 at different levels in mature and immature T-cell subsets. Our data also indicate that mouse macrophages contain the regulatory factors necessary to transcribe the human CD4 gene.
Mol Cell Biol 1994 Feb
PMID:Specific expression of the human CD4 gene in mature CD4+ CD8- and immature CD4+ CD8+ T cells and in macrophages of transgenic mice. 828 89

The double negative (CD4-CD8-) alpha beta+ T cells constitute about 20% of all alpha beta+ T cells in murine lungs. We find that in BALB/c mice 60% of the double negative alpha beta+ pulmonary T cells express receptors of the V beta 8 family whereas only 33% of single positive (CD4+/CD8+) pulmonary T cells express V beta 8. However, in C57BL/6 mice, equal frequencies (25%) of double negative and single positive alpha beta+ pulmonary T cells express V beta 8. The high frequency of double negative V beta 8+ pulmonary T cells is dominantly inherited in (C57BL/6 X BALB/c) F1 offsprings. Further studies exclude the involvement of classic MHC region genes in determining the level of V beta 8 usage among double negative pulmonary T cells. Upon exposure to mycobacterial antigens, double negative alpha beta+ pulmonary T cells are co-enriched in vitro in parallel with gamma delta+ T cells.
Am J Respir Cell Mol Biol 1994 Jan
PMID:Selection of pulmonary CD4-, CD8-, alpha beta+ T cells expressing V beta 8 T cell receptors. 829 84

CD8+ T cells predominate in the lungs in hypersensitivity and human immunodeficiency virus-related lymphocytic pneumonitis, but their role in the immunopathogenesis of lung disease is unknown. We have shown that in immunized mice depleted of CD4+ T cells, CD8+ T cells are recruited into the lungs in response to intratracheal antigen challenge with sheep red blood cells (SRBC) (J. Clin. Invest. 1991; 88:1244-1254) or to pulmonary infection with Pneumocystis carinii (Am. J. Respir. Cell Mol. Biol. 1991; 5:186-197), suggesting that recruitment of CD8+ T cells does not depend on CD4+ T cell-derived signals. Because CD8+ T cells themselves produce a variety of chemotactic and immunoregulatory cytokines, CD8+ T cells may be important participants in, and modulators of, pulmonary immune responses. To test this hypothesis, we examined the effects of CD8+ T cell depletion on the generation of a pulmonary immune response in vivo. We monitored the recruitment of mononuclear cells into lungs in the absence of CD8-dependent signals and measured the duration of pulmonary inflammation in the absence of suppressor CD8+ T cells. Primed mice were treated with anti-CD8 monoclonal antibody to deplete CD8+ T cells and subsequently were challenged intratracheally with 5 x 10(8) SRBC. At various times after challenge, total and differential cell counts and lymphocyte phenotypes were measured in bronchoalveolar lavage fluid by flow cytometry and lungs were scored histologically. We found that depletion of CD8+ T cells neither decreased recruitment of immune and inflammatory cells nor prolonged the pulmonary immune response.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1993 Jul
PMID:Pulmonary lymphocyte recruitment: depletion of CD8+ T cells does not impair the pulmonary immune response to intratracheal antigen. 833 79

Expression of the human CD8 alpha gene is restricted to cells of the lymphoid lineage and developmentally regulated during thymopoiesis. As an initial step towards understanding the molecular basis for tissue-specific expression of this gene, we surveyed the surrounding chromatin structure for potential cis-acting regulatory regions by DNase I hypersensitivity mapping and found four hypersensitive sites, three of which were T cell restricted. By using a reporter-based expression approach, a T-cell-specific enhancer was identified by its close association with a prominent T-cell-restricted hypersensitive sites in the last intron of the CD8 alpha gene. Deletion studies demonstrated that the minimal enhancer is adjacent to a negative regulatory element. DNA sequence analysis of the minimal enhancer revealed a striking cluster of consensus binding sites for Ets-1, TCF-1, CRE, GATA-3, LyF-1, and bHLH proteins which were verified by electrophoretic mobility shift assays. In addition, the 5' end of the enhancer was composed of an Alu repeat which contained the GATA-3, bHLH, and LyF-1 binding sites. Site-directed mutation of the Ets-1 and GATA-3 sites dramatically reduced enhancer activity. The functional importance of the other binding sites only became apparent when combinations of mutations were analyzed. Taken together, these results suggest that the human CD8 alpha gene is regulated by the interaction of multiple T-cell nuclear proteins with a transcriptional enhancer located in the last intron of the gene. Comparison of the CD8 alpha enhancer with other recently identified T-cell-specific regulatory elements suggests that a common set of transcription factors regulates several T-cell genes.
Mol Cell Biol 1993 Nov
PMID:Identification and characterization of an Alu-containing, T-cell-specific enhancer located in the last intron of the human CD8 alpha gene. 841 95

Murine natural killer (NK) cells express a few antigens not found on other leukocyte subsets. The NK1.1 antigen, that is present in only a few mouse strains, has been extensively characterized whereas our knowledge of the NK2.1 antigen, which is more commonly expressed, remains, as yet, limited. Our laboratory has previously reported the production of a mAb (4LO3311) recognizing a murine NK cell-specific molecule with a similar strain distribution as the NK2.1 antigen formerly defined with an NZB anti-BALB/c antiserum. In this study, we demonstrate by sequential immunoprecipitation that 4LO3311 represents the first NK2.1 antigen-specific mAb. This reagent was used to immunoprecipitate the NK2.1 antigen from 125I-labeled lysates of fresh NK-enriched spleen cells. SDS-PAGE analyses revealed that the NK2.1 antigen is expressed at the cell surface as a N-glycosylated disulfide-linked protein dimer with approximately 65 kD subunits. The NK2.1 antigen is likely to be anchored in the plasma membrane by a peptide moiety since its expression on NK cells was not affected by treatment with phosphatidylinositol-specific phospholipase C. In addition to be present on a splenic NK cell subset, the NK2.1 antigen is shown to be expressed by a small number of CD4-CD8-thymocytes and by a subset of CD4-CD8-IgG- lymph node cells. Finally, it is shown here that unlike the NKR-P1, the rat homologue of the murine NK1.1 antigen, neither the NK2.1 nor the NK1.1 antigen is expressed by polymorphonuclear leukocytes.
Mol Immunol 1993 Sep
PMID:The murine NK2.1 antigen: a 130 kD glycoprotein dimer expressed by a natural killer cell subset of the spleen, thymus and lymph nodes. 841 23

At least three stages in the intrathymic development of pre-T cells are demarcated by differences in the competence to express the interleukin-2 (IL-2) gene as an acute response to stimulation. IL-2 inducibility appears to be acquired relatively early, prior to T-cell receptor (TcR) gene rearrangement. It is then abrogated during the stage when cells are subject to positive and negative selection, i.e., the fate determination processes that select cells for maturation or death. IL-2 inducibility finally reappears in mature classes of thymocytes that have undergone positive selection. To provide a basis for a molecular explanation of these developmental transitions, we have examined the representation in different thymocyte subsets of a set of DNA-binding proteins implicated in IL-2 gene regulation. As the DNA-binding activities of many factors are elicited only by inductive stimuli, the cells were cultured in the presence or absence of the calcium ionophore A23187 and phorbol ester. Our results separate these factors into four regulatory classes: (i) constitutive factors, such as Oct-1 and probably Sp1, that are expressed in thymocytes at all stages; (ii) inducible factors, such as NF-kappa B and complexes binding to the region of a CD28 response element, that can be activated in all thymocytes, including those cells (CD4+ CD8+ TcRlow) that can undergo selection; (iii) inducible factors, such as NF-AT and AP-1, that can be activated in mature (CD4+ CD8- TcRhigh) and immature (CD4- CD8- TcR-) thymocytes alike but not in the transitional stages when the cells (CD4+ CD8+ TcRlow) are subject to selection; and (iv) a factor containing CREB, which can be activated in thymocytes of all developmental stages by culture but does not require specific induction. These results verify that inducible transcription factors are targets of intrathymic developmental change. They also identify NF-AT and AP-1 as factors that are particularly sensitive to the mechanism altering thymocyte responses during the stages when thymocytes may undergo positive and negative selection.
Mol Cell Biol 1993 Jan
PMID:Molecular basis for developmental changes in interleukin-2 gene inducibility. 841 28

We have generated a soluble form of the CD8 molecule consisting of the entire extracellular domains of the human alpha chain, by expressing a mutated CD8 alpha cDNA in SF9 cells infected with a recombinant baculovirus. The truncated molecule was secreted into the medium mostly as a disulfide-linked homodimer in which a single cysteine residue in the hinge-like region (Cys143) was sufficient to assure covalent bonding. Soluble CD8 purified to homogeneity appears to be monodisperse as assessed by gel filtration analysis and contains only O-linked carbohydrates. To determine whether recombinant CD8 can interact with MHC class I molecules, we developed an assay that measures binding of MHC class I-bearing cell lines to purified CD8 adsorbed to plastic plates. The level of binding of cells to immobilized CD8 depended on the amount of CD8 bound to the plate and correlated with the levels of cell surface MHC class I expression. The binding was specifically inhibited by monoclonal antibodies directed either against CD8 or MHC class I molecules. This assay therefore provides a way to measure CD8 binding to MHC class I independently of other cell-cell interactions and should allow direct structure-function studies.
Mol Immunol 1993 Jan
PMID:A soluble form of the human CD8 alpha chain expressed in the baculovirus system: biochemical characterization and binding to MHC class I. 841 75

A new cell proliferation analysis by flow cytometry was applied to the mitogen induced cultures of peripheral blood mononuclear cells (PBMC) from either normal, healthy donors or those individuals who are infected by human immunodeficiency virus, type 1 (HIV-1). While phytohemagglutinin (PHA) stimulation of normal PBMC (nPBMC) yielded propagation of both CD4 (nCD4) and CD8 (nCD8) T cell subsets, similar activation of PBMC from certain HIV-1-infected individuals (HIV-PBMC) produced active proliferation of CD8 (HIV-CD8) cells but varying degrees of CD4 (HIV-CD4) cell destruction. However, no measurable viral p24 antigen was produced extracellularly. On the other hand, when the purified HIV-CD4 cells were similarly activated, no such cell death was noted and high titer p24 was detected in the culture supernatants. Addition of exogenous IL-2 to either HIV-PBMC or HIV-CD4 cultures, did not alter either CD4 cell death or HIV-1 p24 production. Isolated HIV-CD8 killed not only HIV-CD4 but also nCD4, when co-cultured and less proliferative fractions of CD4 cell population was the more preferred targets of the HIV-CD8 CTL activity. The presence of anti-CD4 CTL activity was closely associated with high CD8, but not with CD4 counts, of the HIV+ patients.
Cell Mol Biol (Noisy-le-grand) 1995
PMID:Anti-CD4 cytotoxic T lymphocyte (CTL) activity in HIV+ patients: flow cytometric analysis. 857 41

This is the first time, to our knowledge, that evidence is presented showing that a polyantigenic immunomodulator (PAI), acting as a biological response modifier, can either induce or suppress HIV expression depending on the viral load of infected PBMC. PAI consists of a mixture of inactivated bacteria with influenza virus vaccine. PBMC from HIV-infected patients (asymptomatic, age 22-36, symptomatic, age 30-59 and pediatric, < 2 years old) were co-cultured with PHA-stimulated PBMC from uninfected individuals in medium containing IL-2 and PAI. Parallel co-cultures were carried out in a PAI-free medium. Cultures were fed with PHA-stimulated PBMC from uninfected donors on a weekly basis. HIV-p24 ag and cytokine profiles (IL-1 beta, IL-2, IL-4, IFN-gamma and TNF-alpha) were determined on supernatants on day 14. Peripheral blood samples from each patient were evaluated at the beginning of the experiment as to total CD3, total CD19, CD3/CD4, CD3/CD8, CD16/CD56, CD8/HLA-DR and CD8/CD38 markers through flow cytometry. PAI was able to induce viral expression (up to 11,881 pg/ml of p24 antigen) in cultures showing a low (less than 16 pg/ml) or no viral titer. In contrast, in those cultures with high viral titer (10(2)-10(5) pg/ml), a substantial reduction on the titer was observed upon exposure to PAI. PAI was able to induce the production of IFN-gamma and TNF-alpha while that of IL-4 and IL-1 beta was reduced. The predominant cell type detected in the blood samples of the studied subjects were CD8+, CD8+/CD38+ or CD8+/HLA-DR+.(ABSTRACT TRUNCATED AT 250 WORDS)
Cell Mol Biol (Noisy-le-grand) 1995
PMID:Changes in viral expression and cytokine profile induced by a polyantigenic immunomodulator in HIV-infected peripheral blood mononuclear cells. 857 53


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>