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)

CD8+ (suppressor/cytotoxic) lymphocytes block replication of HIV-1 or the simian immunodeficiency virus of macaques (SIVmac) in PBL of infected individuals. We now show that these CD8+ lymphocytes undergo clonal expansion in vivo after AIDS virus infection of the individual, suggesting they may be antigen-specific T cells. These CD8+ cells block replication of virus in autologous but not MHC class I-mismatched PBL. The inhibitory lymphocytes express the integrin family molecule 4B4 and the CTL-associated S6F1 epitope of LFA-1. Finally, physical contact is required for the CD8+ lymphocyte-mediated inhibition of AIDS virus replication, since this inhibitory function is blocked by anti-LFA-1 and anti-CD8 mAbs. These studies suggest that the cell that inhibits AIDS virus replication in PBL of infected individuals is a CTL.
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PMID:A cytotoxic T lymphocyte inhibits acquired immunodeficiency syndrome virus replication in peripheral blood lymphocytes. 278 86

The phenotype and functions of monocytes in patients with haemophilia A and age-matched controls were studied. Fourteen male haemophiliacs were classified in three categories according to the mean number of units of factor VIII received during the last 5 years. Eleven patients were positive for antibodies to human immunodeficiency virus but none of our patients were homosexuals or drug abusers, nor do they fulfill the criteria of acquired immunodeficiency syndrome. Patients treated with high amounts of factor VIII concentrates (greater than 3 x 10(5) U/year) showed a significantly lower percentage of monocytes expressing HLA-DR, LFA-1 and CR3 antigens as compared with patients receiving lower amounts of factor VIII (less than 2 x 10(6) U/year) or controls. Kinetics of DR, LFA-1 and CR3 in cultured monocytes showed tht they were lost faster by monocytes from haemophiliacs treated with large amounts of factor VIII than by control monocytes. Adherence ability and chemotactic response of monocytes from patients treated with less than 3 x 10(5) U/year of factor VIII were also impaired. Although phagocytic indices were in normal ranges in haemophiliacs, a significant difference was observed between percentages of phagocytic monocytes from haemophiliacs treated with the largest doses of factor VIII and normal controls. Tests for respiratory burst activity, measured by chemiluminescence and superoxide anion generation, and Staphylococcus aureus killing were in normal ranges in haemophiliacs' monocytes.
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PMID:Phenotypic and functional abnormalities in monocytes from patients with haemophilia A treated with factor VIII concentrates. 282 91

The functional role of the LFA-1 molecule in the interaction between helper T lymphocytes and B lymphocytes was investigated using lymphocytes from patients with leukocyte adhesion deficiency, an inherited immunodeficiency characterized by a defective leukocyte expression of the LFA-1, Mac-1 (CR3) and p150,95 molecules. The ability of LFA-1- T lymphocytes to provide antigen-specific help for HLA-identical LFA-1+ B lymphocytes was reduced while their antigen-specific activation was normal. Antigen-independent conjugate formation between resting, nonactivated LFA-1- T lymphocytes and LFA-1+ B lymphocytes was impaired while LFA-1- B lymphocytes bound LFA-1+ T lymphocytes normally. Conjugate formation of activated LFA-1- T lymphocytes was mostly mediated by the CD2-LFA-3 adhesion pathway while the ICAM-1 molecule, a ligand of LFA-1, had no function. These results demonstrate that LFA-1 plays a major role in the cognate interaction between helper T lymphocytes and B lymphocytes that cannot be mediated instead by CD2 or other molecules on resting T lymphocytes.
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PMID:The role of lymphocyte function-associated antigen 1 (LFA-1) in the adherence of T lymphocytes to B lymphocytes. 304 49

Activation of the enzyme protein kinase C (PKC) plays an important role in T cell activation. We investigated the phosphorylation of CD2, CD3, CD4, CD5, CD7, CD8, CD28 (Tp44), CD43 (sialophorin, gp115), and LFA-1 after incubation of human PBMC with the (PKC) activator PMA. These proteins were chosen for their role in transmembrane signal transduction (CD2, CD3, CD5, CD28, CD43), cell-cell interaction and adhesion (CD2, CD4, CD8, and LFA-1), or involvement in immunodeficiency states (CD43, CD7). CD5, CD7, CD43, and the alpha-chain of LFA-1 were found to be constitutively phosphorylated. PMA induced rapid hyperphosphorylation of CD5, CD7, and CD43, but not of the LFA-1 alpha-chain, and induced the phosphorylation of CD3, CD4, CD8 and of the LFA-1 beta-chain. PMA did not cause the phosphorylation of CD2 and CD28. PMA-induced phosphorylation was partially inhibited by the PKC inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine dihydrochloride. Finally, the T cell activator Con A, which binds to the CD3/TCR complex was shown to induce a profile of protein phosphorylation similar to that observed with PMA. We conclude that PKC-mediated phosphorylation of T cell Ag may represent an important regulatory mechanism that governs the process of T cell activation.
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PMID:Phosphorylation of T cell membrane proteins by activators of protein kinase C. 325 10

Monocytes in a familial monocyte disorder, a recently recognized primary immunodeficiency syndrome, with impaired phagocytic functions were studied for their ability to produce interleukin 1 (IL-1) as well as the surface property. Monocytes from two children (siblings) with the disorder possessed CD11b, CD13, CD14, CD33, Ia and LFA-1/Mac-1/p150,95 beta subunit antigens as determined by flow cytometry. Electron microscopic cytochemistry showed that the monocytes had surface glycoproteins reactive with four representative lectins. The IL-1 production by monocytes was assayed in the two patients and compared with that in six children with primary immunodeficiency syndromes and some monocyte abnormalities; three had congenital neutropenia, two had hyper-IgE syndrome, and one had defective monocyte chemotaxis. Monocyte culture supernatants were prepared with stimulation by lipopolysaccharide or silica, and their IL-1 activity was measured by the mouse thymocyte-proliferation assay. The patients' monocytes were defective in IL-1 production: the values were less than 1.0% of the control monocyte values (n = 12) and were in contrast with those of congenital neutropenia monocytes of 186.2% to 204.3%. These results demonstrate a familial monocyte disorder which is characteristic among the immunodeficiency syndromes with regard to the defective IL-1 production and the impaired phagocytic functions.
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PMID:Defective interleukin-1 production in a familial monocyte disorder with a combined abnormality of mobility and phagocytosis-killing. 326 74

Four children with an immunodeficiency involving the absence of leukocyte membrane glycoproteins reacting with anti-LFA-1 and OKM-1 monoclonal antibodies were unable to mediate adherence-dependent leukocyte functions. Even with normal Fc receptor function, their PMN-ADCC and MC-NKC were markedly deficient. Single cell analysis demonstrated deficient antibody-mediated PMN-target cell adherence. Monoclonal antibodies against LFA-1 and OKM-1 reproduced this immunodeficiency in leukocytes from normal adults. LFA-1/OKM-1 mediates a PMN-target cell adhesive step.
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PMID:Defective natural killer cytotoxicity and polymorphonuclear leukocyte antibody-dependent cellular cytotoxicity in patients with LFA-1/OKM-1 deficiency. 609 61

We have shown that a monoclonal antibody to the cell surface adhesion molecule LFA-1 (CD18/CD11a) enhances plasma neutralization of a laboratory isolate (HIVMN) and a primary isolate (HIV28R) of human immunodeficiency virus type 1. Human phytohemagglutinin blasts were infected with HIVMN or HIV28R in the presence of plasma pooled from HIV-positive individuals (AIDS plasma) or immunoglobulin G from AIDS plasma alone or combined with a monoclonal antibody (MAb) to LFA-1. While AIDS plasma alone at a dilution of 1:1,250 neutralized HIVMN and HIV28R infection by 15 and 0%, respectively, in the presence of a saturating concentration of the MAb to LFA-1 the plasma neutralized both viruses by more than 80% at this dilution. Immunoglobulin G purified from AIDS plasma, when used in combination with the MAb to LFA-1, showed the same synergistic effect in HIV neutralization as seen with the AIDS plasma and anti-LFA-1. The MAb against LFA-1 partially neutralized both viral isolates (45 to 55%) on its own. These results demonstrate significant synergy between the plasma and antibody against LFA-1 in the neutralization of HIV. The observations therefore suggest an important role for adhesion molecules in HIV infectivity and transmission. The results have implications for the recently observed host effect on HIV susceptibility to antibody neutralization.
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PMID:Antibody to adhesion molecule LFA-1 enhances plasma neutralization of human immunodeficiency virus type 1. 754 42

The promonocytic human leukemic cell line U937, when infected with lymphotropic human immunodeficiency virus type 1 (HIV-1), becomes a continuous virus producer. A total of 46 U937-derived subclones in suspension was isolated and classified into three (2 high, 42 middle, and 2 low) types based on their susceptibility to the infection. By analyzing subclones before infection, we found that the high-type subclones expressed LFA-1 antigens at a relatively low level. In addition, the ability of these subclones to induce adherence after exposure to phorbol 12-myristate 13-acetate (PMA) was reduced. In contrast, a transition by HIV-1 infection to adherent macrophage-like cells was induced only in the high-type, but not in the low-type subclones. The high-type adherent cells obtained by HIV-1 infection were followed by further lineage to become retrodifferentiated suspension cells showing reduced syncytia formation ability. Superoxide was generated in the high-type subclones, without PMA-mediated differentiation, from the early stage of infection before HIV-1 replication, as well as during undifferentiated, differentiated and retrodifferentiated stages. In contrast, it was only transiently generated at acute phase of HIV-1 replication in low-type subclones. Long-term culture of the low-type subclones decreased the expression of major structural viral protein Gag and also virus production. Thus, the mechanism by which PMA differentiates U937 cells is not the same as that induced by HIV-1 infection. The latter mechanism results in high susceptibility to infection. The HIV-1 phenotypes of finally obtained persistently infected cells were also affected by the cell stages at the time of infection.
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PMID:High susceptibility of U937-derived subclones to infection with human immunodeficiency virus type 1 is correlated with virus-induced cell differentiation and superoxide generation. 759 17

We have previously shown that lymphocytic cells bind to cultured syncytiotrophoblast and that this may be important in the lymphocyte-mediated infection of trophoblast with the human immunodeficiency virus (HIV). Leukocyte-trophoblast adhesion may also have implications for normal trophoblast function. The following experiments were designed to characterize the adhesion systems that mediate the attachment of lymphocytic cells to trophoblast. Adhesion was assayed by labelling lymphocytic MOLT-4, clone 8 cells with the fluorescent marker, calcein-AM, and then incubating them with primary cultures of human syncytiotrophoblast. Adhesion was stimulated by pretreatment of the trophoblast cultures with several cytokines either alone or together. These included tumor necrosis factor-alpha (TNF-alpha), granulocyte/macrophage-colony stimulating factor (GM-CSF), interleukin-1 beta (IL-1 beta) and interferon-gamma (IFN-gamma). Stimulation was time- and dose-dependent. In contrast, preincubation of trophoblast cultures with anti-TNF-alpha antibodies for 2 days reduced MOLT adhesion by almost 50%. Preincubation with other anti-cytokine antibodies had no significant effect on adhesion. In other experiments, adhesion was measured in the presence of antibodies to known adhesion molecules. Adhesion was reduced by 50% in the presence of antibodies to alpha 4 integrin or beta 1 integrin. When present together, these antibodies reduced adhesion by almost 85%. Incubation in the presence of antibodies to the very late activation antigen-4 (VLA-4; alpha 4 beta 1 integrin) counter-receptors, VCAM-1 and CS-1, was without effect. Adhesion was also unaffected by antibodies to LFA-1, ICAM-1, ICAM-2, LFA-2, or LFA-3. These results suggest that adhesion is mediated by an adhesion system consisting of lymphocyte VLA-4 (alpha 4 beta 1) and an as yet unidentified counter receptor on trophoblast.
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PMID:Effect of cytokines and anti-adhesion molecule antibodies on the adhesion of lymphocytic cells to human syncytiotrophoblast. 780 71

The intercellular adhesion molecule (ICAM-1, CD54) and its counter receptor, the integrin leukocyte function associated antigen 1 (LFA-1, CD11a/CD18), have important roles in the immune response. These include guiding leukocytes to sites of inflammation (Issekutz and Issekutz, 1992), enhancement of antigen presentation (Moy and Brian, 1992) and potentiation of cytotoxic cell function (Umehara et al., 1992; Sanchez-Madrid et al., 1982). In addition to these activities LFA-1 and ICAM-1 are implicated in the cell-to-cell transmission of human immunodeficiency virus (HIV-1) since antibodies to CD18, CD54 or synthetic peptide analogs of ICAM-1 antagonise the formation of virus-induced syncytia (Fecondo et al., 1993; Gruber et al., 1991; Hildreth and Orentas, 1989; Valentin et al., 1990). The alpha-glucosidase 1 inhibitor 6-O-butanoyl castanospermine (MDL 28574) has antiviral activity for HIV which is manifested by a decrease in syncytia as well as the production of virus with altered gp120 and a reduced infectivity (Taylor et al., 1991). Previously, it has been shown that the alpha-glucose 1 inhibitor (MDL 28574) treatment of human leukocytes in vitro or mouse lymphocytes in vivo affects the detection of LFA-1 but not domain 1 of CD4 nor several other CD markers (Bridges et al., submitted for publication). Here, we demonstrate that pre-treatment of HIV-permissive CD4+ cells with MDL 28574 substantially reduces their capacity to bind with cells chronically infected with HIV-1 which results in reduced virus production.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The prevention of cell adhesion and the cell-to-cell spread of HIV-1 in vitro by the alpha-glucosidase 1 inhibitor, 6-O-butanoyl castanospermine (MDL 28574). 784 78


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