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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cell surface markers CD4, CD8, Leu8 and Leu15 (CD11) were used to separate human lymphoid cell subsets with monoclonal antibody-coated immunomagnetic beads. We show that each of these subsets is able to suppress the induction of IL-2 and IFN-gamma genes effectively. This is manifested by a pronounced superinduction of IL-2 and IFN-gamma mRNA, as well as IFN-gamma protein, in cell populations depleted of one of these subsets. Co-culture of cell subsets with total cell populations or depleted ones, on the other hand, leads to severe inhibition of expression of these genes. In these experiments, cells in suppressor subsets exhibit little, if any, expression of IL-2 and IFN-gamma genes. By contrast, depending on donor and lymphoid tissue examined (tonsils or peripheral blood mononuclear cells), CD4, CD8, Leu8, and Leu15 cell subsets are also able to express IL-2 or IFN-gamma genes to high levels. Moreover, in Leu8+ cells that do not express the IFN-gamma gene, extensive expression of both mRNA and protein can be elicited by inhibiting the activation of suppressor cells with gamma-irradiation before induction. These results support the concept that the potential to express or suppress human IL-2 and IFN-gamma genes is not restricted to distinct cell subsets. Suppression or expression can be elicited in cells carrying a given surface marker, depending on the state of the immune system in a lymphoid tissue.
Mol Immunol 1990 Dec
PMID:The potential to express or suppress human interleukin-2 and interferon-gamma genes is not restricted to distinct cell subsets. 170 79

We have investigated by flow cytometry the action of dextran sulfate (DxS) on the expression of the LFA-1 molecule in human lymphocytes. This work was undertaken because of the involvement of the LFA-1 molecule in HIV-1 induced syncytia and because of the role of DxS played in the inhibition of syncytia formation. Firstly we detected five distinct topographic regions (epitopes) on the LFA-1 molecule with a panel of 11 monoclonal antibodies (Mabs). Then we demonstrated that DxS interacts with some epitopes mainly present on the alpha chain of the LFA-1 molecule. This inhibition on the LFA-1 expressions by DxS occurs after 1-3 hr of incubation of either 4 or 37 degrees C with complete reappearance of LFA-1 within 1 hr of placing cells in fresh medium. In addition both 5 and 500 kDa have been found to have a similar influence on the inhibition of the LFA-1 expression, while non sulfated dextran have no effect. Other sulfated polyanion (SP) such as heparin and chondroitin sulfate have no effect on the LFA-1 expression. Further at 4 degrees C, DxS does not alter the expression of molecules recognized by Mab such as Leu3a (CD4), Leu2a (CD8), Leu4 (CD3) and Leu5b (CD2). However at 4 degrees C, DxS decreases the expression of CD45R molecule which is recognized by Mab Gap8.3. At 37 degrees C, we observe a decrease also in CD4 expression after DxS exposure. It has also been found that DxS decreases LFA-1 expression to the same extent regardless of the basal expression of LFA-1 in each selected cell subset (LFA-1 low, dim or bright). These results suggest that the inhibitory effect of DxS on the HIV-induced syncytium formation could be due partially to a specific steric hindrance of some LFA-1 determinants.
Mol Immunol 1991 Oct
PMID:Dextran sulfate specifically interacts with the human LFA-1 molecule (leucocyte function associated antigen-1). 171 37

A computer graphics molecular model of the C terminus of gp120 of HIV has been constructed using predicted secondary structure based on homologies with proteins for which X-ray crystallographic data have been published. The model shows sequences known to be important in CD4 binding in close proximity to regions with a high probability of forming alpha helical and beta strand motifs. The orientation adopted by these domains approximates to the known 3D structure of HLA-A2 alpha 2 chain without constraints based on HLA-A2 as a template being introduced. The model may therefore represent an energetically favourable conformation for a part of gp120 which mimics the binding domain for the T-cell receptor on MHC molecules. Recognition of gp120 as an alloepitope in high affinity association with CD4 would explain many of the sequelae of acquired immune deficiency on HIV infection.
Mol Aspects Med 1991
PMID:A proposed molecular model for the carboxy terminus of HIV-1 gp120 showing structural features consistent with the presence of a T-cell alloepitope. 172 16

Glucocorticoid (GC) treatment is known to induce destruction of cortical thymocytes and then their reconstitution. By using the rats treated with GC, we examined the relationship between rosette-formation and surface markers (CD4 and CD8) for clarifying the processes of differentiation and maturation in rat thymocytes. Thymus weight and thymocyte count began to decrease immediately after GC administration and became minimal on 5-7 days, followed gradual recovery. The percentage of rosette-forming thymocytes began to decrease immediately after GC treatment and became minimal on 5 days, followed by recovery to the normal level by the 10th to 14th day after treatment. During the analysis of the changes in the percentage of 4 subsets (CD4-8-, CD4+8+, CD4+8+, CD4-8+) of rat thymocytes after GC treatment, the percentage of CD4+8+ cells was found to change in close relation to the change in the percentage of rosette-forming lymphocytes, suggesting that rosette-forming thymocytes are CD4+8+ cells. These results suggest that the treatment induces destruction of GC-sensitive thymocytes, possibly rosette-forming cells, followed by migration of precursor T cells (CD4-8- cells) in the thymus, and that the precursors change into rosette-forming cells (CD4+8+ cells) in the thymus, followed by differentiation and maturation into non-rosette-forming cells (CD4+8- or CD4-8+ cells).
Cell Mol Biol 1991
PMID:Surface characteristics of thymocytes in glucocorticoid treated rats using rosette-formation technique and surface marker analysis. 177 21

We have assumed that rat thymocytes capable of rosette-formation with guinea pig erythrocytes were double positive (CD4+8+) cells. Therefore surface-binding erythrocytes on rosette-forming lymphocytes (RFLs), separated in highly pure state, were eliminated by a hypotonic shock. The surface markers of RFLs, without surface erythrocytes, were analyzed by flow cytometry using two kinds of monoclonal antibodies (anti-CD4, anti-CD8) labelled with different fluorescence materials. About 96.2% of cells in the RFL population were sorted in two areas, into which double positive cells were separated. This result substantiates the assumption mentioned above. It was, furthermore, discussed that the RFLs without surface erythrocytes would be one of the valuable materials for disclosing the mechanisms of differentiation and maturation from double positive thymocytes to single positive ones.
Cell Mol Biol 1991
PMID:Surface antigenic analysis of rosette-forming cells in rat thymus--using monoclonal antibodies against T cell surface markers. 180 93

The proviral burden of peripheral blood lymphocytes in 29 patients infected with human immunodeficiency virus type-1 (HIV-1) was estimated using a polymerase chain reaction method which we recently refined. The mean numbers of HIV-1 provirus in eight patients with AIDS and AIDS-related complex treated with zidovudine (AZT), in 10 asymptomatic patients treated with AZT, and in 11 asymptomatic untreated patients were 892, 436, and 406 copies in 1 x 10(5) CD4- T lymphocytes, respectively. These results demonstrate that patients may have more HIV-1 provirus copies in an advanced than early stage of disease, and that the fraction of the infected lymphocytes is much higher than previously thought, especially in asymptomatic patients. There was no difference in the viral burden in CD4+ T lymphocytes regardless of whether AZT had been administered or not. These findings validate the method used here to quantitate HIV-1 provirus DNA and confirm that AZT is not effective in reducing the amount of provirus DNA in lymphocytes.
Mol Cell Probes 1991 Apr
PMID:Quantitative estimation of human immunodeficiency virus type-1 provirus in CD4+ T lymphocytes using the polymerase chain reaction. 183 Jan 29

Glycosphingolipids added to the cell culture medium can be incorporated into the plasma membrane and interfere with the growth of certain cell types. In the past years, previous reports have shown that gangliosides, a class of glycosphingolipids bearing sialic acid can inhibit antigen or mitogen induced T cell proliferative responses in vitro. We report here that the inhibition of PHA induced proliferation by the trisialoganglioside GT1b was not reversed by addition of exogenous IL-1, IL-2, TPA and calcium ionophore. Furthermore, GT1b did not affect IL-2 production by activated T cells. In addition, GT1b ganglioside could also decrease strongly the expression of the T cell antigens CD3, CD2, CD4, CD8 and the alpha/beta T cell receptor antigenic complex whereas it did not affect HLA-class I antigens. By contrast, GT1b modulated only partially membrane expression of activation antigens such as CD25 (Tac) and transferrin receptor and increased the expression of HLA-class II antigens. Moreover CD25 messenger RNA induction was not affected by GT1b treatment of PHA-stimulated T cells. Our results demonstrate that gangliosides, in spite of their anti-proliferative capacity and their modulation effect on T cell antigen membrane expression, do not prevent the progression of T cells into early stages of the activation process.
Mol Immunol 1991 Nov
PMID:Analysis of phenotypic and functional changes during ganglioside-induced inhibition of human T cell proliferation. 183 57

Cytotoxic T lymphocytes (CTL) specific for autologous human melanoma have been successfully generated in vitro from tumor bearing lymph nodes without any stimulation by the autologous tumor. Tumor-involved lymph node cells (LNC) were cultured in serum free medium (AIM-V) containing 1,000 U/ml of recombinant interleukin-2. The best expansion and specific cytotoxicity of CTL were achieved in 4 to 6 weeks of culture. The predominant populations in cultured LNC-derived CTL were CD2+, CD3+, CD4-, CD8+, CD56-, and HLA-DR+ T cells. These data suggested that tumor-involved LNC may provide an alternative source for the generation of tumor-specific CTL in adoptive immunotherapy.
Mol Biother 1991 Jun
PMID:Generation of human autologous melanoma-specific cytotoxic T cells from tumor-involved lymph nodes. 191 Jun 25

Expression of the CD4 and CD8 glycoproteins is a tightly regulated process tied to the maturation of functionally distinct classes of thymocytes. Therefore, understanding of the mechanism of expression of the genes encoding CD4 and CD8 is likely to yield important insight into regulation of the differentiated functions of T cells. Here, we report the identification of a T-cell-specific enhancer in a DNase I-hypersensitive region about 13 kb 5' of the transcription initiation site of the murine CD4 gene. Within the minimal enhancer element, at least three nuclear protein binding sites were identified by DNase I footprint analysis. One site contains the consensus motif for TCF-1 alpha/LEF-1, a recently identified HMG box transcription factor primarily expressed in pre-B and T cells. By Southwestern (DNA-protein) blotting and binding competition analyses, the protein binding to this site was found to be indistinguishable from TCF-1 alpha/LEF-1. Mutagenesis of this site resulted in loss of factor binding but had a relatively minor effect on enhancer activity. In contrast, mutations in another site, containing two consensus binding motifs for basic helix-loop-helix proteins, abolished factor binding and dramatically reduced enhancer activity. None of the protein binding sites had activity on its own, suggesting that the CD4 enhancer requires the interaction of multiple regulatory sites.
Mol Cell Biol 1991 Nov
PMID:Identification and characterization of a T-cell-specific enhancer adjacent to the murine CD4 gene. 192 61

The CD4 molecule is a relatively non-polymorphic 55 kDa glycoprotein expressed on a subset of T lymphocytes. A common African allele of CD4 has been identified by non-reactivity with the monoclonal antibody, OKT4. The genetic basis for the OKT4- polymorphism of CD4 is unknown. In the present paper, the structure of the CD4 molecule from an homozygous CD4OKT4- individual was characterized at the molecular level. The size of the CD4OKT4- protein and mRNA were indistinguishable from those of the OKT4+ allele. The polymerase chain reaction (PCR) was used to map the structure of CD4OKT4- cDNAs by amplifying overlapping DNA segments and to obtain partial nucleotide sequence after asymmetric amplification. PCR was then used to clone CD4OKT4- cDNAs spanning the coding region of the entire, mature CD4 protein by amplification of two overlapping segments followed by PCR recombination. The nucleotide sequence of CD4OKT4- cDNA clones revealed a G----A transition at bp 867 encoding an arginine----tryptophan substitution at amino acid 240 relative to CD4OKT4+. Expression of a CD4OKT4- cDNA containing only this transition, confirmed that the arginine----tryptophan substitution at amino acid 240 ablates the binding of the mAb OKT4. A positively charged amino acid residue at this position is found in chimpanzee, rhesus macaque, mouse and rat CD4 suggesting that this mutation may confer unique functional properties to the CD4OKT4- protein.
Mol Immunol 1991 Nov
PMID:A single amino acid substitution in a common African allele of the CD4 molecule ablates binding of the monoclonal antibody, OKT4. 196 Nov 96


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