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

The MHC class II CID represents an example of immunodeficiency in which the defect in expression of membrane glycoproteins leads to abnormal cell to cell interactions and thus to abnormal immune responses. It represents an interesting model which confirms the importance of MHC molecules in all immune responses to foreign antigens. It also underlines the complexity of regulatory mechanism which control the expression of MHC class II genes. To elucidate these mechanisms, it is essential to identify and characterize the genes involved in control of MHC class II expression.
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PMID:Combined immunodeficiency with abnormal expression of MHC class II genes. 246 26

In this report we have attempted to review our knowledge of the role(s) of CD4 in human T-cell function and the consequences of interactions between CD4 molecules and the human immunodeficiency virus (HIV). The observation in 1981 that antibodies to certain epitopes of CD4 inhibited the immune functions of CD4+ T cells led to the initial suggestion that CD4 molecules play a direct role in T-cell function. Although the precise functions of CD4 remain incompletely understood, a preponderance of evidence suggests that this molecule may in fact serve several critical roles. At least one such role is that of interacting directly with MHC class II molecules on antigen-presenting cells, presumably facilitating cell-to-cell interactions. On activated CD4+ T cells, CD4 molecules can also interact directly with the T-cell receptor complex to influence the immune response. Unfortunately, in addition to interacting with the T-cell receptor and class II MHC determinants, CD4 serves as a high affinity receptor for HIV, the causative agent of AIDS. Not only does interaction between the virus and CD4 initiate viral fusion to the cell membrane and HIV entry but, in addition, a similar molecular interaction initiates fusion between HIV-infected and uninfected CD4+ cells, resulting in the formation of multinucleated syncytia. Since uninfected CD4+ cells are, in effect, recruited into such syncytia, this mechanism may account in part for the depletion of CD4+ T cells in HIV-infected patients. Soluble forms of CD4 produced either by genetic engineering or solid phase peptide synthesis can completely block HIV infectivity and syncytia formation in vitro, remarkably without apparent effects on T-cell immunity. Such molecules are currently being explored for their possible therapeutic effects on HIV infection in vivo.
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PMID:Role of CD4 in normal immunity and HIV infection. 247 27

The human cell surface protein CD4 is not only an important accessory molecule in the activation of MHC class-II-restricted T cells, but has also been implicated to be a receptor for the human immunodeficiency virus HIV-I on lymphoid and monocytic cells. We have found that a 24-h treatment of the promonocytic leukemia cell line U937 with rIFN-gamma decreases the expression of the CD4 Ag by 50% as measured by cytofluorographic analysis. The decrease in CD4 expression was dependent on the concentration of rIFN-gamma, with maximal effects occurring at 20 to 200 U/ml. The decrease appeared to be due to actual loss of the CD4 molecule from the cell surface rather than masking of a particular epitope, inasmuch as similar results were obtained with the OKT4 and OKT4A antibodies. The effect of rIFN-gamma to decrease CD4 expression was not due to a general loss of cell surface Ag, because the binding of OKM1 and anti-HLe-1 increased after rIFN-gamma treatment. Treatment of rIFN-gamma also decreased cell surface CD4 expression on the promyelocytic leukemia cell line HL-60, and on the monocytic cell line THP-1, although the extent of the decrease was less than on U937 cells. Freshly isolated normal peripheral blood monocytes treated for 48 h with rIFN-gamma bound much less OKT4 or OKT4A antibody than cells incubated in the absence of rIFN-gamma. Moreover, treatment with rIFN-gamma reduced the percentage of peripheral blood monocytes that were positive for the CD4 Ag. In contrast with the decrease in CD4 levels on rIFN-gamma-treated monocytes, treatment with rIFN-gamma had no effect on CD4 levels on peripheral blood T lymphocytes or T cell lines.
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PMID:Treatment with recombinant IFN-gamma decreases cell surface CD4 levels on peripheral blood monocytes and on myelomonocyte cell lines. 249 48

MHC class II deficiency is an inherited immunodeficiency disease characterized by the presence of a normal number of T and B lymphocytes and profound anomaly of cellular and humoral responses to foreign antigens. All bone-marrow-derived cells (including B lymphocytes, monocytes and activated T lymphocytes) and also enterocytes and endothelial cells do not express all HLA class II (DR, DQ and DP) molecules on their membrane. It is known that the proper recognition of foreign antigens depends on their presentation, together with HLA class II molecules, on the membrane of antigen-presenting cells. MHC class II deficient combined immunodeficiency confirms the important role of MHC gene products in immune-defence mechanisms. Patients suffer from repeated and severe infections that are frequently the cause of death. The defect in HLA class II expression is the consequence of a lack of synthesis of HLA class II alpha and beta chains in patients' cells. Studies performed at DNA and RNA levels showed that there was no gross abnormality of MHC class II genes and that mRNA for all HLA molecules was not detected in patients' cells. These results, together with segregation studies performed in several families, suggested that the defect in HLA class II gene expression involves a transacting regulatory factor. Direct transcription assays showed that the disease is characterized by an absence of HLA class II gene transcription. An analysis of the specific binding of nuclear proteins from patients' cell lines to HLA class II promotor showed that a specific protein, RF-X, which normally binds to a regulatory sequence common to HLA class II promotors, is affected in MHC class II combined immunodeficiency.
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PMID:Combined immunodeficiency with defective expression in MHC class II genes. 251 9

Lethally irradiated mice transplanted with H-2-matched, minor histocompatibility-disparate bone marrow develop graft-vs-host disease (GVHD) that is associated with severe immunodeficiency. Splenocytes from such mice contain radioresistant cells that profoundly suppress normal lymphocyte function. We now show that GVHD-induced suppressor cells also inhibit the proliferation of CD4+ T cell clones specific for different Ag and class II MHC determinants. These suppressors have a dominant anti-proliferative effect, because they inhibit DNA synthesis in response to receptor-mediated stimulation and growth-promoting lymphokines, without abolishing lymphokine secretion or lymphokine receptor expression by the cloned T cells. The implications of these findings, and the usefulness of T cell clones for studying immune suppression, are discussed.
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PMID:Immunodeficiency in graft-versus-host disease (GVHD). II. Effects of GVHD-induced suppressor cells on CD4+ T cell clones. 252 50

The resting human microglia have previously been shown to be cells of dendritic morphology expressing class II MHC antigens and macrophage specific antigens by immunocytochemical techniques. To examine the relationship between the microglia and the family of dendritic antigen presenting cells (APC), normal white matter from eight normal adults with no neurological disease at autopsy was examined by immunocytochemical techniques to localize antibodies to leukocyte common antigen (LCA), HLA-DR, CD1 (T6), CD4 (T4), and glial fibrillary acidic protein. In addition, enzyme histochemical staining for ATPase, non-specific esterase (NSE), and acid phosphatase (ACP) was performed. The normal microglia are ATPase +ve, NSE -ve, ACP -ve, HLA-DR +ve, LCA +ve, CD1 (T6) +ve and weakly CD4 (T4) +ve. This specialized phenotype closely resembles that of Langerhans cells and suggests that microglia are not simply quiescent phagocytes, but may have a primary role as microenvironmentally specialized APC. The finding of weak anti-CD4 (T4) immunoreactivity supports suggestions for a central role for this cell in infection of the central nervous system by human immunodeficiency virus type 1.
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PMID:Microglial cells in human brain have phenotypic characteristics related to possible function as dendritic antigen presenting cells. 253 Mar 24

The role of direct virus infection as a determining factor in acquired immunodeficiency syndrome (AIDS) dementia was investigated using in situ hybridisation for human immunodeficiency virus (HIV) and human cytomegalovirus (HCMV). Four of the five AIDS dementia patients in this series demonstrated HIV infected cells distributed in widely different parts of the brain, but only one case showed HCMV infected cells. The greater abundance of HIV was in subcortical white matter in nodular areas consisting of monocyte/macrophage infiltrates. The cells were occasionally arranged as a multinucleated syncitium. In two cases, a few large cells with the appearance of neurons were positive for HIV hybridisation. By appropriate treatment with ribonuclease, it was shown that hybridisation was primarily to HIV RNA. HCMV infected cells were observed in small numbers in only one of the positive cases, suggesting that HCMV is not a determining factor in AIDS dementia. HCMV positive cells were located in the grey matter, with an appearance suggestive of neurons. Cells expressing the MHC-class II antigen HLA-DR, a marker of reactive microglia and macrophages, were observed to be extensive in affected brain sections in the one case examined. These cells were present in greater number than HIV infected cells. In this case, extensive numbers of HIV infected cells were noticed along the peripheral margin of the substantia innominata. This could indicate infection in this case of a critical brain region from the cerebrospinal fluid.
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PMID:Examination of brains of AIDS cases for human immunodeficiency virus and human cytomegalovirus nucleic acids. 254 95

A toddler with common variable hypoimmunoglobulinemia (CVH), inflammatory bowel disease, and recurrent Pneumocystis carinii pneumonia (PCP) on intravenous gammaglobulin (IVIG) replacement was evaluated for a combined cellular immunodeficiency. He had a normal number of circulating T-cells, natural killer (NK) cells, T-cell subset percentages, and his peripheral blood mononuclear (PBM)-derived B-cell number was low. PBM mitogen blastogenesis and mixed lymphocyte reaction (MLR) were normal. MLR activated T-cells expressed class I and II MHC antigens, interleukin 2 (IL-2), and B-cell growth factor (IL-5)-related receptors. The patient's T-cells induced control B-cell maturation with pokeweed mitogen (PWM-PC), and did not suppress PWM-PC production by allogeneic PBM. Bone marrow (BM) CD19+ B-cell number varied between 10 and 44% of all PBM, and the BM B-cell-enriched fraction failed to differentiate to PWM-PC with autologous or allogeneic T-cell help. The NK activity assayed using K562 target cells was deficient, 9.2 x 7.7% (6.9-9.2%) pt, control 35.9 x 35.8% (16.3-67.2% +/- 12.8). In the presence of interferon-alpha, 800 U/ml, the patient's NK activity increased to 17.2 x 14.9% (12.6-17.2%), control 35.9 x 51.0% (36.5-72.3% +/- 12.0). The patient's cell-mediated lympholysis of HLA nonidentical, allogeneic stimulators was normal. Maintaining trough serum IgG levels above 500 mg/dl was required to suppress recurrent PCP. This functional NK deficiency may be relevant to the development of recurrent PCP in IVIG-treated CVH patients.
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PMID:Common variable hypogammaglobulinemia, recurrent Pneumocystis carinii pneumonia on intravenous gamma-globulin therapy, and natural killer deficiency. 278 54

The CD4 (T4) molecule is expressed on a subset of T lymphocytes involved in class II MHC recognition, and is probably the physiological receptor for one or more monomorphic regions of class II MHC (refs 1-3). CD4 also functions as a receptor for the human immunodeficiency virus (HIV) exterior envelope glycoprotein (gp120) (refs 4-9), being essential for virus entry into the host cell and for membrane fusion, which contributes to cell-to-cell transmission of the virus and to its cytopathic effects. We have used a baculovirus expression system to generate mg quantities of a hydrophilic extracellular segment of CD4. Concentrations of soluble CD4 in the nanomolar range, like certain anti-CD4 monoclonal antibodies, inhibit syncytium formation and HIV infection by binding gp120-expressing cells. Perhaps more importantly, class II specific T-cell interactions are uninhibited by soluble CD4 protein, whereas they are virtually abrogated by equivalent amounts of anti-T4 antibody. This may reflect substantial differences in CD4 affinity for gp120 and class II MHC.
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PMID:A soluble CD4 protein selectively inhibits HIV replication and syncytium formation. 282 23

The X-linked lymphoproliferative syndrome (XLPS) is an immunodeficiency characterized by severe primary infection with the Epstein Barr (EB) virus, which is often fatal. This has been attributed to failure to generate T lymphocytes which are specifically cytotoxic for EB virus-infected B lymphocytes, and which develop in all normal individuals following primary infection. We have studied a kindred which carried the defective gene for XLPS and have confirmed that the pattern of serum antibody responses to EB viral antigens can be used to detect affected males and female carriers. Furthermore, an EB virus genome-carrying B cell line which grew spontaneously from a culture of bone marrow cells from a male child with XLPS at the time of primary infection showed a decreased sensitivity to MHC-restricted, EB virus-specific killing by a T cell clone when compared to its in vitro EB virus-transformed counterpart. From these results we suggest that a subset of EB virus-infected B lymphocytes which were resistant to EB virus-specific killing existed in this child, and may have contributed to the overwhelming EB virus infection and its fatal outcome.
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PMID:A family study of the X-linked lymphoproliferative syndrome: evidence for a B cell defect contributing to the immunodeficiency. 300 60


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