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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Major histocompatibility complex (MHC) class II deficiency (bare lymphocyte syndrome) is a rare inborn error of the immune system characterized by impaired antigen presentation and combined immunodeficiency. It causes severe and unremitting infections leading to progressive liver and lung dysfunctions and death during childhood. As in other combined immunodeficiency disorders, bone marrow transplantation (BMT) is considered the treatment of choice for MHC class II deficiency. We analyzed the files of 19 patients who have undergone BMT in our center. Of the 7 patients who underwent HLA-identical BMT, 3 died in the immediate posttransplant period of severe viral infections, whereas the remaining 4 were cured, with recovery of normal immune functions. Of the 12 patients who underwent HLA-haplo-identical BMT, 3 were cured, 1 was improved by partial engraftment, 7 died of infectious complications due to graft failure or rejection, and 1 is still immunodeficient because of engraftment failure. A favorable outcome in the HLA-non-identical BMT group was associated with an age of less than 2 years at the time of transplantation. All the patients with stable long-term engraftment had persistently low CD4 counts after transplantation (105 to 650/microL at last follow up), but no clear susceptibility to opportunistic infections despite persisting MHC class II deficiency on thymic epithelium and other nonhematopoietic cells. We conclude that HLA-identical and -haploidentical BMT can cure MHC class II deficiency, although the success rate of haploidentical BMT is lower than that in other combined immunodeficiency syndromes. HLA-haploidentical BMT should preferably be performed in the first 2 years of life, before the acquisition of chronic virus carriage and sequelae of infections.
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PMID:Bone marrow transplantation in major histocompatibility complex class II deficiency: a single-center study of 19 patients. 781 13

Continuing controversy surrounds the cellular effects of the Nef protein of HIV-1, a nonstructural protein expressed by most isolates. Highly purified protein isoforms of MW 27 kDa (Nef 27) and 25 kDa (Nef 25), produced in Escherichia coli by translation from the first and second start codons of HIV-1 nef clone pNL4.3, respectively, were introduced into cells by a sophisticated electroporation technique which uses electric field rather than electric charge to transfer macromolecules across cell membranes. Electroporation of Nef 27 reduced the expression of cell surface CD4 by 30-50%, as measured by flow cytometry, on phytohemagglutinin (PHA)-activated PBMC as well as on a variety of CD4+ T-cell lines (MT-2, CEM, and Jurkat). Reduction in surface CD4 was observed in all cells of the CD4+ T-cell lines but only in the CD4+ cells of the mixed PBMC population. Electroporation of Nef 27 into MT-2 cells and PHA-activated PBMC also reduced the expression of IL-2R to background levels. Other cell surface antigens analyzed such as CD2, CD7, or transferrin receptor (TfR) were not affected by the introduction of HIV-1 Nef 27. In contrast to the effects of Nef 27, electroporation of Nef 25 into cells at equivalent concentrations did not affect the surface expression of CD4 and IL-2R. These data show that the HIV-1 clone pNL4.3 Nef 27 but not the Nef 25 isoform specifically decreases expression of two cell surface receptors important for antigen recognition of MHC class II antigens and for cell proliferation. Production of Nef 27 during HIV-1 infection of cells of the immune system may contribute to immunodeficiency even in the absence of direct viral cytopathic effects.
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PMID:Nef 27, but not the Nef 25 isoform of human immunodeficiency virus-type 1 pNL4.3 down-regulates surface CD4 and IL-2R expression in peripheral blood mononuclear cells and transformed T cells. 790 28

CD4 serves as a receptor for MHC class II antigens and as a receptor for the human immunodeficiency virus (HIV-1) viral coat protein gp120. It is coupled to the protein-tyrosine kinase p56lck, an interaction necessary for an optimal response of certain T cells to antigen. Although anti-CD4 crosslinking may increase lck activity, the effects of HIV-1 gp120 have been controversial. Activated protein-tyrosine kinases are known to associate with certain intracellular proteins possessing src-homology regions (SH-2 domains) such as phosphatidylinositol 3-kinase (PI 3-kinase). In this paper, we demonstrate that the CD4:p56lck complex associates with significant amounts of phosphatidylinositol (PI) kinase activity. High pressure liquid chromatographic (HPLC) analysis of the reaction products demonstrated the presence of phosphatidylinositol 3-phosphate (PI 3-P) and phosphatidylinositol 4-phosphate (PI 4-P), thus indicating that PI 3 and PI 4 kinases associate with CD4-p56lck. The p85 subunit of PI 3-kinase was also detected in anti-CD4 immunoprecipitates by immunoblotting with anti-p85 antiserum. Significantly, p56lck binding to CD4 appears to be necessary for the detection of lipid kinase activity associated with p56lck. Also, anti-HIV gp120 and anti-CD4 crosslinking induced a 10-15-fold increase in levels of both PI 3- and PI 4-kinase activity in anti-CD4 precipitates. Stimulation of CD4-p56lck-linked PI kinases by crosslinked HIV-1 gp120 may play a role in HIV-1-induced immune defects.
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PMID:Regulation of CD4-p56lck-associated phosphatidylinositol 3-kinase (PI 3-kinase) and phosphatidylinositol 4-kinase (PI 4-kinase). 790 44

Based on our findings that HIV-1 (human immunodeficiency virus type 1) soluble gp41 (sgp41; amino acids 539-684) bound to human T, B, and monocyte cells and enhanced major histocompatibility complex (MHC) class I and II antigen expression on Raji cells, we examined the effect of HIV-1 sgp41 on the surface expression of MHC I and II, ICAM-1, and CD4 molecules on human H9 and U937 cells. Flow cytometry (FACS) analysis demonstrated that sgp41 selectively enhanced MHC class I expression by about 75% on H9 cells and by about 85% on U937 cells, while the ICAM-1 expression was increased by about 70% only on H9 cells and remained unaltered on U937 cells; other molecules, such as MHC class II and CD4, remained unaltered. By comparison, alpha-, beta-, and omega-interferons, but not gamma-interferon, showed similar effects as sgp41 on the expression of MHC class I and ICAM-1 on H9 and U937 cells. The results suggest that HIV-1 gp41 may have a biological function that is involved in the regulation of human MHC class I and ICAM-1 expression.
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PMID:HIV-1 gp41 enhances major histocompatibility complex class I and ICAM-1 expression on H9 and U937 cells. 791 56

An extensive genetic and physiological analysis of the cheetah by O'Brien et al. (1983; 1985; 1987) indicated that the cheetah showed monomorphism at the major histocompatability complex. This led O'Brien (1985) to propose that the cheetah suffered from an immunodeficiency and was highly susceptible to diseases. It was therefore decided to investigate cell-mediated and humoral immune responses and to apply the limited restriction fragment length analysis (using Pst 1 and Bam H1 enzymes) of the cheetah MHC I and MHC II genes. Antibody responses to antigens (feline viruses), as well as mitogen-induced lymphocyte blast transformation responses, were shown to be intact and comparable with that of the domestic cat, indicating a competent immune system in the cheetah. It was also suggested by the results that some polymorphism does exist in the MHC class II genes, but possibly not in the MHC class I genes.
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PMID:Lymphocyte blast transformation responses and restriction fragment length analysis in the cheetah. 797 May 77

One of the difficulties in understanding the complex pathology of human immunodeficiency virus (HIV) infection is to explain the progressive depletion of the CD4 helper T cell population and consequently the destruction of the immune system. Although cytopathic effects of HIV are observed in vitro, they cannot in vivo account for CD4 T cell depletion because relatively few cells are productively infected. Thus immunological mechanisms must be envisaged. We have found that peripheral blood lymphocytes (PBLs) from asymptomatic HIV-infected individuals are primed for a suicide process known as apoptosis or programmed cell death (PCD). DNA fragmentation characteristic of apoptosis was enhanced by stimulation of lymphocytes with ionomycin, a known inducer of apoptosis in suitably primed cells. Identification of the T cell subpopulations programmed for apoptosis indicated that both CD4+ and CD8+ cells died when cultured without stimulation or when polyclonally stimulated with ionomycin. Activation-induced cell death was also observed after stimulation with self-MHC class II-dependent superantigens, namely bacterial toxins from Staphylococcus (SEB), Streptococcus (ETA), and Myocoplasma (MAM) and under these conditions the CD4+ T cells were preferentially affected. To explore whether new macromolecular synthesis were required for apoptosis, various known inhibitors of apoptosis such as cycloheximide, cyclosporin A, Zn2+, or EGTA were tested. Activation-induced apoptosis was found sensitive to these inhibitors, indicating an active mechanism, but apoptosis observed in nonstimulated cultures was not, suggesting that these cells already contained the complete machinery for death. Prevention of apoptosis could be obtained in the presence of a mixture of cytokines and the minimal signal necessary for this prevention was IL-1 alpha and IL-2. Finally, a correlation between PCD and AIDS-pathogenesis was suggested by the comparison of lymphocytes from lentivirus-infected primates suceptible (SIV-infected macaques) and resistant (HIV-infected chimpanzees) to AIDS. Altogether our results suggest that, during HIV or SIV infection, PCD may contribute in vivo to the deletion of reactive T cells after antigenic stimulation.
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PMID:Programmed cell death in AIDS-related HIV and SIV infections. 810 39

The ability of a human coreceptor to function in mice was investigated by generating human CD4 (hCD4)-expressing transgenic mice on a mouse CD4-deficient (mCD4-/-) background. From developing thymocyte to matured T lymphocyte functions, hCD4 was shown to be physiologically active. By examining the expansion and deletion of specific V beta T cell families in mutated mice with and without hCD4, it was found that hCD4 can participate in positive and negative selection. Mature hCD4 single positive cells also were found in the periphery and they were shown to restore MHC class II-restricted alloreactive and antigen-specific T cell responses that were deficient in the mCD4 (-/-) mice. In addition, these hCD4 reconstituted mice can generate a secondary immunoglobulin G humoral response matching that of mCD4 wild-type mice. The fact that human CD4 is functional in mice and can be studied in the absence of murine CD4 should facilitate studies of human CD4 activity in general and human immunodeficiency virus 1 gp120-mediated pathogenesis in acquired immune deficiency syndrome specifically.
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PMID:Human CD4 restores normal T cell development and function in mice deficient in murine CD4. 814 40

CD4, a cell-surface glycoprotein expressed on a subpopulation of T cells, is the receptor for class II molecules of the major histocompatibility complex (MHC II) and a receptor for the envelope glycoprotein (gp 120) of human immunodeficiency virus-1 (HIV-1). Screening of microbial metabolites for CD4-binding activity using an enzyme-linked immunosorbent assay based on the binding of the CD4-specific monoclonal antibody (mAb), anti-Leu3a, identified a family of compounds comprising several novel polyketides. The parent compound (411F, Vinaxanthone) is a C28 molecule probably arising from a dimerization of two C14 polyketide units. It strongly inhibited the interaction of anti-Leu 3a and that of several other D1/D2 epitope-specific mAb with CD4, but only weakly inhibited the binding of HIV-1 gp120. Binding of a representative MHC class II molecule, HLA-DRB*0401, was also inhibited by 411F with a comparable inhibitory concentration (IC50 = 1 microM). In functional assays 411F inhibited antigen-induced CD4-dependent T cell proliferative responses of peripheral blood mononuclear cells. At the clonal level 411F exhibited selectivity in that the compound inhibited peptide-induced CD4+ T cell proliferative responses but not alloantigen-induced CD8+ T cell proliferation. It is hypothesized that 411F, a polyanionic compound in aqueous solution at neutral pH, inhibits CD4-dependent functions by binding over a broad area of the positively charged amino-terminal D1 and D2 domains implicated in the interaction with MHC II molecules. 411F has the potential for development as an immunosuppressive agent with a novel mechanism of action.
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PMID:A fungal metabolite which inhibits the interaction of CD4 with major histocompatibility complex-encoded class II molecules. 814 67

Antigen-independent adhesion of resting adult CD4+ CD45RO+ T cells to B lymphocytes has been shown to be transient and can be down-regulated by CD4 major histocompatibility complex (MHC) class II molecule interactions. Conversely, adhesion of adult CD4+ CD45RA+ subpopulation to B cells is not regulated by ligands of CD4. We have investigated the regulation of adhesion of cord blood CD45RA+ CD4+ T lymphocytes. In contrast to adult CD45RA+ CD4+ T cells, cord blood CD45RA+ CD4+ T cells were strongly sensitive to the down-regulation of adhesion mediated by the CD4-HLA class II interaction, since adhesion to MHC class II(+) B cells was transient and inhibited by an anti-CD4 antibody. In addition, human immunodeficiency virus gp160, synthetic gp106-derived peptides encompassing a CD4 binding site inhibited conjugate formation between cord blood CD45RA+ CD4+ T cells and B cells. Following activation of the cord blood CD4 T cells by an anti-CD3 antibody, a conversion from a transient to a stable adhesion pattern of cord blood CD4 T cells to B cells occurred in 2 days. The reversal to a transient adhesion occurred at day 8 following anti-CD3 activation in correlation with a complete shift to a CD45RO phenotype of the cord blood CD4 T cells. These data suggest that CD4 T cell adhesion can be developmentally regulated.
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PMID:Antigen-independent adhesion of CD4 CD45RA T cells from cord blood. 825 26

Transcription of major histocompatibility complex (MHC) class II genes is controlled largely by the conserved promoter elements called the X and Y boxes. We show here that RFX, the X box-binding protein deficient in certain MHC class II-deficient immunodeficiency patients (CID), and the Y box-binding protein NF-Y bind cooperatively. Functional relevance of this protein-protein interaction is suggested by the fact that promoter activity correlates with cooperative binding of RFX and NF-Y rather than with binding of RFX or NF-Y alone. Stability of the RFX/NF-Y complex is affected by alterations in X-Y box spacing. These results are consistent with the fact that MHC class II promoter function is dependent on correct stereospecific alignment of the X and Y boxes. Cooperative binding involving RFX, NF-Y, and perhaps other MHC class II promoter-binding proteins may explain why the highly specific defect in binding of RFX observed in CID cells is associated in vivo with a bare promoter in which all of the cis-acting elements, including the X and Y boxes, are unoccupied.
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PMID:Function of major histocompatibility complex class II promoters requires cooperative binding between factors RFX and NF-Y. 829 May 61


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