Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been hypothesized that the progressive deletion of CD4+ T cells in the course of infection due to human immunodeficiency virus (HIV) may be mediated in part by interaction with a superantigen inherent in an HIV protein. Consequently, selective loss of CD4+ cells with a T cell receptor V beta-chain capable of interaction with superantigen would produce a CD4+ population less or totally unresponsive to superantigen such as staphylococcal enterotoxins B and A (SEB and SEA respectively), but not to other mitogens such as concanavalin A, anti-CD3 (OKT3), or pokeweed mitogen. We tested this hypothesis by comparing the proliferative response of SEB and SEA with the other mitogens for 25 controls, 20 HIV+, and 15 donors with acquired immune deficiency syndrome (AIDS). We found that peripheral blood mononuclear cells, as well as the CD4+ and CD8+ subsets from both HIV+ and AIDS sources, the degree of suppression of mitogenesis for SEB and SEA was approximately equal to or less than that of the other mitogens. Moreover, suppression of HIV+ CD4+ and CD8+ T cell responses to SEB and SEA was equal (26%). If HIV superantigens exist, our data suggest that they are not responsible for the selective depletion of the CD4+ T cell subset as evaluated by SEB and SEA specificity.
 ...
PMID:Proliferative response of CD4+ and CD8+ T cell subsets from Hispanics with HIV+ and AIDS: the superantigen hypothesis. 790 21

To study the functional integrity of T cells from human immunodeficiency virus type 1 (HIV-1)-infected persons, CD4+ and CD8+ cells were examined for proliferation and secretion of interleukin-2 (IL-2) in response to staphylococcal superantigens and antibodies to CD3 and the alpha beta T cell receptor. A functional defect within CD8+ but not within CD4+ cells from HIV-1-infected persons was observed. Within CD8+ cells, proliferation and secretion of IL-2 was restricted to cells expressing the costimulatory molecule CD28. Such cells were proportionally reduced in HIV-1-infected persons. In patients with advanced immunodeficiency, however, evidence of functional derangement was found also within the CD28+ CD8+ cells. In a cross-sectional study of 73 HIV-infected persons and 15 controls, a significant correlation was observed between the number of CD28+ CD8+ cells and the presence of HIV-related disease. Our results suggest that regulation of expression of CD28 may play an important role in the immunopathogenesis of AIDS.
 ...
PMID:Expression of costimulatory molecule CD28 on T cells in human immunodeficiency virus type 1 infection: functional and clinical correlations. 790 40

CD4, a T cell receptor for major histocompatibility complex class II antigen, is a key regulator of immunological reactivities. When engaged together with the T cell antigen receptor, CD4 enhances immune reactions, whereas when ligated independently of the antigen receptor CD4 inhibits the activation of T cells or initiates their deletion. CD4 serves also as a receptor for the human immunodeficiency virus (HIV), which binds the receptor with high avidity through its envelope molecule, gp120. Studies in tissue culture have shown that its affinity to CD4 gives the virus opportunities to utilize CD4-mediated signaling and to manipulate immunocytes. We show here in human CD4 transgenic mice that appropriately cross-linked HIV envelope protein causes massive deletion of HIV-reactive T cells in vivo.
 ...
PMID:Deletion of T lymphocytes in human CD4 transgenic mice induced by HIV-gp120 and gp120-specific antibodies from AIDS patients. 791 36

A number of endogenous mouse mammary tumor virus (MMTV) proviruses encode superantigen that have the ability to stimulate T cells with a certain T cell receptor (TCR) beta-chain variable region (V beta) and to mediate the V beta-specific clonal deletion. The tumorigenic milk-borne MMTV carried by C3H and GR mice also have superantigenic properties in vivo. In the present study we identified and characterized a novel V beta 8.2-specific superantigen of exogenous MMTV carried by FM mice. The open reading frame (ORF) in the 3' long terminal repeat of the MMTV was cloned by polymerase chain reaction with primers corresponding to conserved regions spanning the ORF coding region. Sequence analysis of the ORF revealed that there is no sequence identical to those in other known MMTV in the carboxy terminus implicated in TCR V beta recognition. Subcutaneous injection of the virus into adult BALB/c mice induced an approximately three- to fourfold enlargement of draining lymph nodes and a substantial increase of V beta 8.2+ CD4+ T cells in the lymph nodes within 6 days. The exposure of newborn BALB/c mice to the virus by foster nursing resulted in a marked deletion of V beta 8.2+ cells both in CD4+ and CD8+ T cells. Thus, a novel milk-borne MMTV in FM mice expresses strong superantigenic properties capable of stimulating V beta 8.2+ T cells. V beta 8.2+ T cells have been demonstrated to be frequently involved in recognition of conventional antigens and responsible for autoimmune diseases such as experimental allergic encephalomyelitis. Therefore, the MMTV (FM) may provide a new mouse model system for inducing immunodeficiency or autoimmune disease by retroviral infection.
 ...
PMID:A V beta 8.2-specific superantigen from exogenous mouse mammary tumor virus carried by FM mice. 791 38

We recently demonstrated that 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) prevented the infection of T cells by human immunodeficiency virus type-1 (Cardin et al., J. Biol. Chem. 266, 13355, 1991). In the present study we have used a panel of monoclonal antibodies (mabs) against a variety of human leukocyte antigens to characterize the interaction of DIDS by flow cytometry with various T cell surface molecules. DIDS blocked the specific immunoreactivity of mabs OKT4A and Leu 3A with CD4 on human leukemic T cells (JM) and human mononuclear lymphocytes with an IC50 approximately 30 microM. The membrane distal (D1) and proximal (D3 and D4) domains of CD4 remained blocked for up to 5 hr of culture and returned to control levels of expression after 24 hr, reflecting the rate of membrane turnover of the CD4-DIDS complex. The binding frequencies (% positive) for anti-CD2, -CD3, -CD5, -CD6, -CD7, -CD8, -CD11a, -CD14, -CD18, -CD19, -CD45, -T cell receptor, and -HLA-DR were not significantly affected. However, there was a partial reduction in the antigen density of CD2, CD5, CD8, and CD11b. The selective interaction of DIDS with CD4 suggests that antagonism of the virus receptor may account in part for the antiviral properties of the stilbene disulfonate.
 ...
PMID:Specific interaction of 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid with human cellular CD4. 795 38

We performed limiting dilution culture of T cells from a patient affected by primary immunodeficiency as a result of complete lack of adenosine deaminase (ADA) activity and also affected by insulin-dependent diabetes mellitus (type I diabetes). Despite the occurrence of immunodeficiency, we were able to raise and grow T cell clones derived from this patient in long-term culture. These T cells displayed ADA enzymatic activity and produced interleukin-2 after engagement of their T cell receptor (TCR)/CD3 complex. We analyzed the TCR repertoire of such clones by nucleotide sequencing of TCR beta chains. The results show that the T cell clones express different V beta but similar J regions. However, the CDR3 regions which are implicated in antigen recognition were found to be heterogeneous.
 ...
PMID:Long-term culture and T cell receptor analysis of T cell clones isolated from a patient with adenosine deaminase deficiency and type I diabetes. 795 66

Surface expression of the CD4 glycoprotein molecule is postulated to facilitate antigen recognition through the T cell receptor (TCR) and is itself a receptor for human immunodeficiency virus (HIV)-gp120 glycoprotein. Both antigen-stimulated TCR activation and HIV infectivity can be blocked by whole anti-CD4 antibodies. Although selective modulation of CD4 from the surface by gangliosides (GM1) blocks HIV infectivity, it enhances associated TCR function. Enhanced TCR function has also been observed after intracellular delivery of synthetic CD4 mRNA-antisense oligodeoxynucleotides (ODN) that block de novo synthesis of CD4. These specific CD4 modulations were mechanistically different from one another yet they both selectively removed the CD4 molecule from the T cell surface and enhanced antigen-stimulated function through the TCR. The proposed role of CD4 during TCR function and HIV infectivity was developed, in part, according to decreases following CD4 antagonism by whole antibody or down-modulation of CD4 by phorbol-stimulated protein kinase C activity. Selective CD4 modulations have independently redefined the specific contributions of CD4 surface expression during T cell activation and may establish a role for CD4 receptor subtypes during HIV-1 infection of CD4+ cells.
 ...
PMID:Understanding the CD4 molecule: surface expression and function. 805 86

The human T cell receptor was studied using an anchored-polymerase chain reaction (A-PCR) and hybridization with V beta-specific oligonucleotide probes, together with the few anti-V beta monoclonal antibodies (mAb) available. After confirming the semiquantitative and reproducible nature of the A-PCR technique, we assessed the complete V beta repertoire in sorted CD4+ and CD8+ lymphocyte populations from three normal donors. These experiments confirmed the absence of V beta-restricted deletions in human peripheral cells, in contrast to several mouse strains. This feature makes it difficult to study negative selection in man, given the apparent absence of an endogenous superantigen corresponding to the Mls system in the mouse. To investigate human V beta repertoire shaping, we studied V beta usage in CD4+ and CD8+ T cells from children with an inherited immunodeficiency characterized by defective expression of human leukocyte antigen class II molecules. An initial study using anti-V beta monoclonal antibodies failed to show significant abnormalities in V beta usage. Four patients analyzed using the A-PCR method all had a polyclonal V beta repertoire, suggesting normal positive selection and raising questions as to the importance of V beta major histocompatibility complex (MHC) interactions and the role of thymic MHC density in shaping the V beta repertoire.
 ...
PMID:Normal T cell receptor V beta usage in a primary immunodeficiency associated with HLA class II deficiency. 809 85

To investigate the possibility of super-antigen-mediated deletions of T cells expressing particular T cell receptor V beta (TcR V beta) gene segments during human immunodeficiency virus (HIV) infection, TcR V beta usage in CD4+ and CD8+ subsets was analyzed in a cohort of infants maternally infected by HIV and in a group of healthy neonates. We used a semi-quantitative anchored polymerase chain reaction technique together with cytofluorographic analysis with anti-V beta monoclonal antibodies. The representation of the 24 V beta families in CD4+ and CD8+ T cells from normal neonates was very similar to that in adults. Preferential expression of V beta 2 in the CD4+ subset was observed in both the neonates and in healthy adults. The representation of the 24 V beta families in peripheral CD4+ T cells from the HIV-infected infants showed no selective V beta deletion, even when the CD4+ subset was globally depleted. Moreover, the main characteristics of the control group (predominance of certain V beta families and V beta 2 skewing towards the CD4+ subset) were also present in all the HIV-infected infants.
 ...
PMID:Lack of selective V beta deletion in peripheral CD4+ T cells of human immunodeficiency virus-infected infants. 810 2

Langerhans cells (LC) belong to the dendritic cell family and represent the principal antigen presenting cells populating squamous epithelia. We have reported the presence of human immunodeficiency virus Type 1 (HIV-1) proviral DNA and RNA in purified LC from the epidermis of seropositive patients. The aim of this study was to quantify HIV-1 proviral DNA in LC of infected patients using a competitive polymerase chain reaction (PCR) assay. Bulk epidermal cell (EC) suspensions were obtained from the skin of nine AIDS patients and six seronegative subjects. Purified LC and LC-depleted EC were prepared by immunomagnetic separation using an anti-CD1a monoclonal antibody. LC preparations did not contain T cells, as assessed by reverse transcription PCR analysis of the T cell receptor beta-chain gene (C region). In addition, no CD14+ cells could be detected in LC fractions by immunostaining of cytospin preparations. To quantify HIV-1 DNA, a new competitive PCR system was devised using SK145/150 as primers (gag) and a competitor plasmid DNA with a modified sequence (209 instead of 142 bp). The number of HIV-1 DNA copies found in the LC of AIDS patients ranged from 107 to 3,645/10(5) LC. In contrast, LC-depleted EC from the same subjects were all negative. The results indicate that in AIDS patients the frequency of infected LC is comparable to that reported for peripheral blood CD4+ T cells.
 ...
PMID:Quantitation by competitive PCR of HIV-1 proviral DNA in epidermal Langerhans cells of HIV-infected patients. 810 64


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