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Results for “CD4 Antigens”

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At least 19 recordsLinked to original sources
PubMed1987

Species heterogeneity in macrophage expression of the CD4 antigen.

The CD4 antigen is expressed on T cells of all mammalian species examined and appears to play an important role in the response of T cells to antigen. In humans, the molecule acts as a receptor for the AIDS virus. Previous studies have demonstrated that M phi in the rat and human also express the CD4 antigen, which is indistinguishable from that on T cells. In this paper we demonstrate by FACS analysis, Northern blot hybridization, and immunoperoxidase labeling that, in striking contrast to the rat and human, mouse M phi do not express the CD4 (L3T4) antigen. This species heterogeneity indicates that T cells and M phi regulate CD4 antigen expression independently and that CD4 may not be essential for M phi function.

Animals↗
PubMed1996

Molecular basis of T lymphocyte CD4 antigen functions.

The T cell surface antigen CD4 plays a pivotal role in the MHC class II-restricted response of specific T lymphocytes and serves as the major receptor of human immunodeficiency viruses (HIV). Recent studies have shown the high complexity of CD4 functions in physiological and pathological conditions. We report here a short review of recent developments in the field and discuss the structural features which regulate the functions mediated by the CD4 coreceptor in mature T lymphocytes.

Binding Sites↗
PubMed1998

Cutting edge: novel RNA ligands able to bind CD4 antigen and inhibit CD4+ T lymphocyte function.

The value of high affinity-specific reagents in immunology is exemplified by the use of mAbs. Recent in vitro selection methods suggested that oligonucleotides may provide a useful alternative, especially where Abs have been insufficient thus far. We used a systematic evolution of ligands by exponential enrichment (SELEX) procedure to derive high affinity oligonucleotide ligands (aptamers) recognizing CD4. These RNase-resistant aptamers bound with high affinity and specificity as demonstrated using BIAcore (Stevenage, U.K.) technology. They also bound native CD4 on rat lymphocytes and specifically interfered with labeling by high affinity mAbs. All aptamers recognized the same binding site in the CDR2-like region in domain 1 of CD4. The applicability of these aptamers for immunologic studies was clearly demonstrated by their ability to block a fully allogeneic MLR in a CD4-specific manner. The high affinity and stability of aptamers point to their value in the analysis and functional manipulation of the immune system.

Animals↗
PubMed2005

Treatment of a patient with a nodal peripheral T-cell lymphoma (angioimmunoblastic T-Cell lymphoma) with a human monoclonal antibody against the CD4 antigen (HuMax-CD4).

A patient with a CD4+ refractory peripheral T-cell lymphoma (PTL), subtype angioimmunoblastic T-cell lymphoma (AILD), was treated with a human monoclonal anti-CD4 antibody (HuMax-CD4) iv once weekly for 10 wk. Early during treatment all palpable enlarged lymph nodes disappeared. A decline of normal CD4+ T-cells in the blood mirrored the treatment effect. Shortly after stopping treatment the patient relapsed with new enlarged lymph nodes. This time no antitumor effect was seen when HuMax-CD4 treatment was reinstituted. No severe side effects were observed during the antibody treatment. This case report is the first describing that HuMax-CD4 has antilymphoma activity in PTL and is an interesting drug to study further in patients with CD4+ PTL.

Aged↗
PubMed1998

Determination of CD4 antigen density on cells: role of antibody valency, avidity, clones, and conjugation.

The number of R-phycoerythrin (R-PE)-conjugated antibodies bound to a cell can be quantitated on a flow cytometer by using beads with known numbers of attached R-PE molecules (QuantiBRITE PE). Using these reference beads, we have observed that a number of factors affect the accuracy of the quantitation and conclusions about epitope density. These factors include valence of antibody binding, the use of antibody fragments (Fab's) versus intact monoclonal antibodies (mAb's), fixation, the purity of the conjugate (i.e., percentage of 1:1 ratios), dissociation rate, the use of washed versus unwashed preparations, and the location of epitope on target antigen. We used CD4 on T cells as a model to explore these challenges in detail. We conclude that CD4+ T cells bind approximately 49,000 CD4 (Leu 3a) antibody molecules, that this binding is bivalent, and therefore that there are approximately 98,000 CD4 antigen molecules on the surface of these cells.

Antibodies, Monoclonal↗
PubMed1992

Down-regulation of lymphocyte CD4 antigen expression by administration of anti-CD4 monoclonal antibody.

Modulation of surface CD4 antigen expression was assessed by flow cytometry after calibration with 125I-labeled anti-CD4 monoclonal antibodies (mAbs). Three patients with severe psoriasis treated with BB14 (anti-CD4 mouse IgG1) and five patients with rheumatoid arthritis treated with BL4 (anti-CD4 mouse IgG2a) were analyzed for sequential changes in surface CD4 expression on CD4+ blood lymphocytes. Anti-CD4 mAb treatment induced a decrease of 50 to 80% of CD4 expression, with slow and partial recovery after cessation of mAb administration. CD4 modulation was related to mAb dosage and mAb concentration in plasma. It was achieved at nonsaturating concentration. In vitro incubation of blood mononuclear cells induced CD4 modulation of similar kinetics and magnitude, associated with decrease of 5-10% of CD3 expression. CD4 modulation required both an intact Fc part of the antibody and the presence of monocytes. The possible role of CD4 modulation should be considered along with other functional activities of anti-CD4 mAbs in analyzing the mechanisms of the clinical effects of these antibodies.

Antibodies, Monoclonal↗
PubMed1998

Production of monoclonal antibody to CD4 antigen and development of reagent for CD4+ lymphocyte enumeration.

A hybridoma secreting monoclonal antibody (mAb) specific to CD4 protein was generated. This monoclonal antibody, named MT4, was proved to be specific to CD4 protein as it reacted with CD4-DNA transfected COS cells, CD4+ cell lines and CD4+ lymphocytes. Furthermore, MT4 mAb inhibited the binding of standard CD4 monoclonal antibodies to CD4 proteins on CD4+ cells. To develop a home made reagent for CD4+ lymphocyte determination by flow cytometry, fluorescein isothiocyanate (FITC) was conjugated to MT4 mAb. To evaluate the developed reagent, 30 HIV infected and 30 healthy individuals were determined for CD4+ lymphocytes by using both a commercial Simultest reagent kit and home made FITC labeled MT4 mAb simultaneously. The study has shown that both percentages and absolute CD4+ lymphocyte counts obtained from both reagents were equivalent. The correlation coefficient for regression analysis was 0.995 and 0.996 for percentages and absolute CD4+ lymphocyte counts, respectively. The results suggest that home made FITC labeled MT4 reagent is an acceptable alternative reagent for monitoring CD4+ lymphocytes in blood samples by flow cytometry.

Animals↗
PubMed1990

Elevated levels of CD4 antigen in sera of human immunodeficiency virus-infected populations.

CD4 antigen levels in sera from asymptomatic intravenous drug users and homosexuals and patients with lymphadenopathy, acquired immunodeficiency syndrome-related complex, or acquired immunodeficiency syndrome were quantitated. Like soluble CD8, CD4 antigen levels were elevated in human immunodeficiency virus-seronegative asymptomatic intravenous drug users and homosexuals, probably reflecting infections such as cytomegalovirus, Epstein-Barr virus, and hepatitis B virus infections. The sera from human immunodeficiency virus-seropositive groups of patients with human immunodeficiency virus infection also had elevated levels of CD4 antigen, presumably reflecting infections like cytomegalovirus and human immunodeficiency virus infections.

AIDS-Related Complex↗
PubMed2000

Molecular modeling on human CCR5 receptors and complex with CD4 antigens and HIV-1 envelope glycoprotein gp120.

AIM: To investigate the interaction between human CCR5 receptors (CCR5) and HIV-1 envelope glycoprotein gp120 (HIV-1 gp120) and HIV-1 receptor CD4 antigens (CD4). METHODS: The structurally conserved regions (SCR) of human CCR5 was built by the SYBYL/Biopolymer module using the corresponding transmembrane (TM) domain of bacteriorhodopsin (bR) as the template. The coordinates for amino-terminal residue sequence, and carboxyl-terminal residue sequence, extracellular and cytoplasmic loops were generated using LOOP SEARCH algorithm. Subsequently the structural model was merged into the complex with HIV-1 gp120 and CD4. RESULTS: Human CCR5 interacted with both an HIV-1 gp120 and CD4. The N-terminal residues (especially Met1 and Gln4) of human CCR5 contacted with CD4 residues, mainly with one span (56-59) of CD4 in electrostatic interaction and hydrogen-bonds. The binding sites of human CCR5 were buried in a hydrophobic center surrounded by a highly basic periphery. On the other hand, direct interatomic contacts were made between 7 CCR5 residues and 6 gp120 amino-acid residues, which included van der Waals contacts, hydrophobic interaction, and hydrogen bonds. CONCLUSION: The interaction model should be helpful for rational design of novel anti-HIV drugs.

CD4 Antigens↗
PubMed2006

Immunogold detection of CD3 and CD4 antigens in patients with Mycosis fungoides.

In this study, we analyzed the distribution of CD3 and CD4 antigens at the ultrastructural level in tissue samples from mycosis fungoides patients using double-immunogold labeling. We observed clusters composed of CD3 and CD4 antigens on the plasma membrane and intracellular. There were also clusters only of one type of the antigen and we could observe more often CD4 than CD3. Labeling of CD3 and CD4 was not found in control cells incubated with non-immune serum. In conclusion, our ultrastructural studies not only visualized pattern distribution and relationship between CD3 and CD4 antigens but might also suggest that the type and form of distribution provides new clues to their possible translocation in mycosis fungoides cells.

CD3 Complex↗
PubMed1991

Growth of human immunodeficiency virus I in cultured cells in the absence of the CD4 antigen.

The ability of a variety of epithelial, embryonal, placental, and neuronal cells to express the CD4 antigen and to be infected by human immunodeficiency virus 1 (HIV-1) was examined. Only two (IMR-32 and HeLa-T4) expressed CD4 detectable by indirect immunofluorescence, and both were infectable by HIV-1. Two others, a human laryngeal carcinoma (HEp-2) and human colonic carcinoma (HT-29), did not express CD4 antigen but were infectable by HIV-1. Infection of the HEp-2 cells was detectable four months (and 20 serial passages) later. Infection of HEp-2 cells was not inhibited by anti CD4 monoclonal antibody but was by the lectin concanavalin A. These results suggest the presence of a receptor other than CD4 can be involved in HIV-1 infection.

Animals↗
PubMed1991

Opposing effects of protein tyrosine kinase inhibitors on the monoclonal antibody induced internalization of CD3 and CD4 antigens.

We have previously demonstrated that the monoclonal antibody (mAb)-induced modulation of CD3 and CD4 antigens from the surface of human peripheral blood lymphocytes is not dependent from protein kinase C activity (Thuillier et al., Eur. J. Immunol. 1990. 20:1197). In the present report we study the effect of genistein and of herbimycin A, two potent inhibitors of protein tyrosine kinases (PTK), on the mAb-induced modulation of CD3 and CD4 surface antigens. Both genistein and herbimycin inhibited the mAb-induced internalization of CD3 and, in contrast, facilitated that of CD4 antigen. These results indicate that the mAb-induced modulation of CD3 is essentially dependent on the PTK pathway, whereas PTK appear to negatively regulate the mAb-induced modulation of CD4.

Antibodies, Monoclonal↗
PubMed1994

Soluble CD8 and soluble CD4 antigens in viral hepatitis and alcoholic cirrhosis.

Serum levels and production of soluble CD8 and soluble CD4 antigens by peripheral blood mononuclear cells were determined in patients with alcoholic cirrhosis and acute or chronic viral hepatitis. Patients with chronic viral hepatitis had significantly increased soluble CD8 serum levels (n = 18; 734 +/- 143 U/ml) (mean +/- SD) compared to healthy controls (n = 80; 312 +/- 141 U/ml; p < 0.001) and patients with alcoholic cirrhosis (n = 12; 505 +/- 256 U/ml; p = 0.006), whose soluble CD8 concentrations were also higher than controls (p < 0.001). In contrast, soluble CD4 antigen serum levels were similar in all groups. In addition, patients with chronic hepatitis showed an increased production of soluble CD8, but not soluble CD4, after mitogenic stimulation of their peripheral blood mononuclear cells compared to controls or patients with alcoholic cirrhosis. Patients with acute viral hepatitis, studied within the first 2 weeks after onset of jaundice, showed markedly elevated serum concentrations of soluble CD8 (n = 4; 807 +/- 379 U/ml; p < 0.001 vs. controls), but not soluble CD4. In addition, nine patients with chronic hepatitis C were studied during and after treatment with alpha interferon. Soluble CD8 serum concentrations of six treatment responders were not found to be different from the low levels seen in controls, whereas three non-responders had increased soluble CD8 levels which were similar to levels in untreated patients with chronic hepatitis C. After interferon-alpha therapy ended, a significant elevation of soluble CD8 serum concentrations was observed in four relapsing patients, which paralleled the serum ALT increase.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Modulation of CD4 antigen expression on human gingival Langerhans cells by gamma interferon.

Human gingival organ culture was used to test the hypothesis that gamma interferon (gamma-IFN), which induces HLA-DR and HLA-DQ antigens on Langerhans cells, modulates CD4 antigen expression on these same cells. Before culture, the density of CD4+ cells in the gingival epithelium was 12.7% +/- 3.8% of the density of CD1+ cells. gamma-IFN (200 IU/ml) enhanced CD4 expression such that at 24 h, all CD1+ cells also expressed CD4. Prostaglandin E2, which in isolation had no effect, partially abrogated the stimulatory effect of gamma-IFN on CD4 expression. These results imply that gamma-IFN and prostaglandin E2 are two signals which regulate CD4 expression on gingival Langerhans cells.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1993

Down-regulation of CD4 molecules by the expression of Nef: a quantitative analysis of CD4 antigens on the cell surfaces.

Nef is one of the non-structural genes encoded by human immunodeficiency viruses. The protein product is associated with the cellular and plasma membranes, and is synthesized soon after entry of the virus. However, little is known about its functions relevant to viral replication and cytopathogenesis. CD4 is considered to be a crucial molecule for the signal transduction and maturation of T cells, and also serves as the receptor for HIV-1. It has been suggested that the down-regulation of cell surface CD4 by Nef proteins is somehow controversial. In order to evaluate the effects of Nef on the CD4 molecule, we constructed a CD4+ monocytoid cell line in which the HIV-1 nef gene was placed under the transcriptional control of the human metallothionein IIA promoter. The analysis of this cellular clone showed that CD4 on the cell surface was down-regulated when Nef proteins were induced. The amount of CD4 antigens on the cell surface correlated inversely with the level of Nef protein expression. This down-regulation of CD4 antigens by Nef was found to occur at the post-translational level. These results showed that the nef gene could modulate the pathophysiology of AIDS by altering the surface CD4 expression.

Blotting, Southern↗
PubMed1995

Soluble CD4 antigen reactivity in intravenous immunoglobulin preparations: is it specific?

Soluble CD4 antigen (sCD4) was measured in seven commercially available intravenous immunoglobulin preparations (IVIg) by means of a double determinant immunoassay (DDIA), whereby two MoAbs recognizing two distinct and spatially distant epitopes on CD4 were used to capture and detect the antigen, respectively. Preincubation of six out of seven IVIg, which were found to be apparently positive for sCD4, with mouse- and bovine-derived serum or purified immunoglobulins completely neutralized DDIA reactivity for sCD4. The inhibition was specific since it was not or only partially observed when IVIg were mixed with whole serum or purified IgG from rabbit. Extensive absorption of six IVIg on insolubilized mouse IgG (mIgG) resulted in a complete loss of reactivity. Eluted human anti-mouse antibodies (HAMA) from any of the IVIg displayed a dose-dependent binding in a DDIA, though its extent varied from one preparation to another. Western blot analysis showed that HAMA from all IVIg contained no component with a molecular weight identical with or close to that of recombinant CD4. Purified mIgG markedly influenced the sCD4 reactivity of two IVIg (Sandoglobulin and Globuman I.V.) when sCD4 was measured with a purchased 'CD4-specific Test Kit', thus suggesting that HAMA can exceed the absorbing capacity of the sample diluent. Taken as a whole, these data indicate that sCD4-based DDIA signal is mostly, if not completely, generated by the presence of human immunoglobulin with anti-mouse immunoglobulin reactivity, thus casting doubts on the actual occurrence of sCD4 in IVIg.

Animals↗