Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Histamine is known to trigger the release of interleukin (IL)-16 from human CD8(+) cells. However, the individual roles of the presently known histamine receptor subtypes (H(1)-H(4)) in this inflammatory response have not been fully characterized. Histamine stimulation of human CD8(+) T lymphocytes purified from peripheral blood led to a 5- to 8-fold increase in the basal release of IL-16 within 24 h, and this increase was significantly blocked by the H(2)-selective antagonist, cimetidine, or by thioperamide, an antagonist of H(3) and H(4) receptors, respectively. The H(1) antagonist pyrilamine showed limited effects. Agonists selective for H(2) (dimaprit), H(3/4) (R-(-)-alpha-methylhistamine), and H(4) (clobenpropit) were capable of inducing the release of bioactive IL-16 because CD8(+) cell supernatants induced CD4(+) cell migration, which was abrogated by an anti-IL-16 antibody. Furthermore, preincubation of lymphocytes with pertussis toxin abolished IL-16 release triggered by activation of the G(i/o)-coupled H(4) receptor but not by the H(2) receptor. Messenger RNA expression studies confirmed H(4), H(2), and H(1) expression in human CD8(+) lymphocytes, whereas H(3) mRNA was completely absent. All leukocyte populations investigated expressed mRNA for H(4), with highest levels found in eosinophils, dendritic cells, and tonsil B cells. H(4) expression was also detected in human lung, trachea, and various cells of human lung origin, such as fibroblasts, bronchial smooth muscle cells, epithelial, and endothelial cells. Since many of those are known sources of IL-16, immune cell- and lung cell-expressed H(4) receptors may have a general role in the control of this mediator of inflammatory disorders such as asthma.
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PMID:Histamine h(4) and h(2) receptors control histamine-induced interleukin-16 release from human CD8(+) T cells. 1223 64

We previously reported that murine experimental allergic encephalomyelitis can be induced by an additional intraperitoneal and intracerebral (i.c.) restimulation in resistant B6 mice after standard immunization with myelin antigens in complete Freund's adjuvant and Bordetella pertussis coadjuvant. Neutrophils infiltrated into perivascular spaces at 12 h, followed by mononuclear cells 24 h after i.c. injection. In this study, we report that the i.c. injection induced the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). The kinetic expression of ICAM-1 or VCAM-1 on brain endothelial cells paralleled the infiltration of neutrophils and mononuclear cells, respectively. The infiltrated lymphocytes also expressed very late antigen-4 (VLA-4) molecules. The microvascular endothelial cells were positive for VCAM-1, whereas the surrounding mononuclear cells were VLA-4 positive. Furthermore, we found a unique subpopulation of cells with characteristics of CD4(-)CD8(-)V(beta)8(+) markers. The kinetic studies of this population showed that these cells were transiently depleted from 12 to 24 h after i.c. challenge (before the development of clinical symptoms) in cervical lymph nodes. These CD4(-)CD8(-)V(beta)8(+) cells can be expanded by in vitro culture with myelin basic protein or IL-2. No significant changes of CD4(+)/CD8(+) cells were noted. CD4(+)CD8(-)CD3(+) cells were also found in brain by double histochemical stains and were the major infiltrating cells at 24 or 48 h after i.c. challenge.
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PMID:Infiltrated Cells in Experimental Allergic Encephalomyelitis by Additional Intracerebral Injection in Myelin-Basic-Protein-SensitizedB6 Mice. 1238 77

We have recently reported that the mean number of CCR5 coreceptors at the surface of CD4(+) T cells (CCR5 density) correlates with viral load and disease progression in HIV-1-infected persons. Here, we definitively establish that CCR5 density determines the level of virus production and identify the stages of HIV-1 replicative cycle modulated by this effect. We show, by transducing the CCR5 gene into CCR5(+) cells, that CCR5 overexpression resulted in an HIV-1 overinfectability. We sorted HOS-CD4(+)-CCR5(+) cells into two subpopulations, HOS(high) and HOS(low), the former expressing seven times more cell surface CCR5 molecules than the latter. Virus production was 30-80 times higher in HOS(high) cells than in HOS(low) cells after a single round of infection. In contrast, only twice as many viral particles entered the cytosol of HOS(high) cells as compared with the cytosol of HOS(low) cells. Yet, seven times as many early, and 24 times as many late, reverse transcription products were found in HOS(high) cells as compared with HOS(low) cells. Moreover, a 24- to 30-fold difference in the number of copies of integrated HIV-1 DNA was observed. No difference in HIV-1 LTR activation between the two cell lines was evident. Finally, we show that the higher virus production observed in HOS(high) cells is inhibited by pertussis toxin, a Galphai protein inhibitor. Thus, CCR5 density mainly modulates postentry steps of the virus life cycle, particularly the reverse transcription. These data explain why CCR5 density influences HIV-1 disease progression and underline the therapeutic interest of lowering CCR5 expression.
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PMID:Cell surface CCR5 density determines the postentry efficiency of R5 HIV-1 infection. 1243 15

Rett syndrome is a progressive neurodevelopmental disorder with a well-defined clinical spectrum and course. Recently, mutations in the gene encoding X-linked methyl-CpG binding protein 2 (MECP2) have been identified as the cause of Rett syndrome. Along with the classic form, variant forms of Rett syndrome and Rett syndrome phenotypes are also recognized. We report on a girl who, at age 2 months, developed an acute encephalopathy with destructive brain damage 12 hours after acellular pertussis vaccination. Peripheral lymphocyte subset analysis revealed the existence of T lymphocytes double positive for CD4 and CD8 markers. This pattern normalized over the following 3 months. Months later, the girl manifested a Rett syndrome phenotype. DNA screening of the MECP2 gene was unrevealing in the child and her parents. This previously unreported association emphasizes the notion that Rett syndrome phenotypes can result from different (either genetic or environmental) causes.
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PMID:Rett syndrome phenotype following infantile acute encephalopathy. 1250 49

Induction of mucosal immunity in the respiratory tract is crucial for protection against respiratory infections. Here, we have investigated the effects of the routes of immunization as well as of three different adjuvants on the induction of mucosal immune responses. Mice were immunized using intranasal (i.n.) or intraperitoneal (i.p.) routes with the mycobacterium PstS-1 antigen. Cholera toxin (CT), detoxified pertussis toxin (detPT) and RU 41.740 from Klebsiella pneumoniae were compared as mucosal adjuvants. Our data showed that i.n. route of immunization induced the most favorable stimulation of mucosal antigen-specific IgA responses supported by mixed Th cells producing IL-4, IL-5, IFN-gamma. In contrast, i.p. immunizations elicited only enhancement of systemic responses, predominantly of the Th2 type. Furthermore, the use of CT as mucosal adjuvant resulted in the stimulation of a mixed Th cell response whereas detPT evoked mainly Th2 type of responses. Likewise CT, the RU 41.740 adjuvant elicited a mixed Th cell response, albeit supported by much lower numbers of CD4(+) T-cells. Thus, i.n. route of immunization favors the induction of mucosal and systemic immune responses, while the Th cell development at mucosal inductive site is influenced by the adjuvant used for immunizations.
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PMID:B- and T-cell responses to the mycobacterium surface antigen PstS-1 in the respiratory tract and adjacent tissues. Role of adjuvants and routes of immunization. 1253 44

Recent experimental evidence shows that vaccination with amyloid-beta peptide (Abeta) of transgenic mouse models of Alzheimer's disease protects from the pathological accumulation of amyloid within the CNS. Phase I/II clinical trials of Abeta vaccination in mild to moderate Alzheimer's disease have been undertaken. Un expectedly, one of these trials has been suspended because 15 patients showed clinical signs consistent with CNS inflammation. Here, we show that C57BL/6 mice immunized with Abeta1-42 peptide develop an inflammatory disease of the CNS characterized by the presence both in the brain and spinal cord of perivenular inflammatory foci containing macrophages, T and B cells, and immunoglobulins. The experimental disease was observed only when pertussis toxin, an agent known to favour autoimmune processes, was co-administered. The immune-mediated CNS reaction was associated to Abeta-induced CD4(+) cells showing a Th1-type cytokine expression profile and to elevated levels of circulating anti-Abeta immunoglobulins. Our results indicate that vaccination with Abeta could determine, under certain circumstances, an aberrant autoimmune-type reaction to Abeta resulting in a perivenular inflammatory encephalomyelitis.
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PMID:Vaccination with amyloid-beta peptide induces autoimmune encephalomyelitis in C57/BL6 mice. 1253 98

Neonatal immaturity of the immune system is currently believed to generally limit the induction of immune responses to vaccine Ags and to skew them toward type 2 responses. We demonstrated here that Bordetella pertussis infection in very young infants (median, 2 mo old) as well as the first administration of whole-cell pertussis vaccine induces B. pertussis Ag-specific IFN-gamma secretion by the PBMC of these infants. IFN-gamma was secreted by both CD4(+) and CD8(+) T lymphocytes, and the levels of Ag-induced IFN-gamma secretion did not correlate with the age of the infants. Appearance of the specific Th-1 cell-mediated immunity was accompanied by a general shift of the cytokine secretion profile of these infants toward a stronger Th1 profile, as evidenced by the response to a polyclonal stimulation. We conclude that the immune system of 2-mo-old infants is developmentally mature enough to develop Th1 responses in vivo upon infection by B. pertussis or vaccination with whole-cell pertussis vaccines.
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PMID:Bordetella pertussis infection in 2-month-old infants promotes type 1 T cell responses. 1253 14

Human immunodeficiency virus (HIV) gp120 induces multiple cellular signaling pathways, including the phosphatidylinositol 3-kinase (PI3-kinase) pathway. The role of the PI3-kinase pathway in HIV-1 replication is not understood. Here we examined whether HIV-1 gp120 upregulates the PI3-kinase pathway and whether PI3-kinase activity plays a role in virus replication in primary human CD4(+) T cells and macrophages. Soluble and virion-associated HIV-1 gp120 induced calcium mobilization and phosphorylation of the PI3-kinase downstream effectors PKB/Akt and p70 S6 kinase. gp120-induced PI3-kinase activity and calcium mobilization were inhibited by pertussis toxin and blocking antibodies directed against CCR5 and CXCR4, suggesting that the signaling is mediated through the chemokine receptor. The PI3-kinase inhibitor LY294002 inhibited infection of CD4(+) T cells and macrophages with X4 and R5 HIV-1-pseudotyped viruses at concentrations that did not induce cell toxicity or downregulate HIV-1 coreceptor expression. When gp120-induced signaling was bypassed with the vesicular stomatitis virus G envelope protein, infection was still sensitive to PI3-kinase inhibition, suggesting that basal PI3-kinase activity is required for infection. LY294002 inhibited HIV-1 infection when added after viral entry and did not affect formation of the HIV-1 reverse transcriptase products R/U5 and long terminal repeat/Gag in the presence of the inhibitor. However, when the inhibitor was added after viral integration had occurred, no inhibition of HIV infection was observed. Our studies show that inhibition of the PI3-kinase signaling pathway suppresses virus infection post-viral entry and post-reverse transcription but prior to HIV gene expression. This type of host-virus interaction has implications for anti-HIV therapeutics that target cellular signaling machinery.
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PMID:Phosphatidylinositol 3-kinase regulates human immunodeficiency virus type 1 replication following viral entry in primary CD4+ T lymphocytes and macrophages. 1255 92

Experimental autoimmune encephalomyelitis (EAE) was induced with myelin oligodendrocyte glycoprotein (MOG(1-125)) in CD4(-/-) and CD8(-/-) DBA/1 mice. Both gene-deleted mice developed clinical signs of EAE, albeit milder than in wild-type mice, suggesting that both CD4(+) and CD8(+) cells participate in disease development. Demyelination and inflammation in the central nervous system was reduced in the absence of CD8(+) T cells. Antibody depletion of CD4(+) cells completely protected CD8(-/-) mice from MOG-induced EAE while depletion of CD8(+) cells in CD4(-/-) mice resulted in fewer EAE incidence compared to that in control antibody-treated mice. Antibody depletion of CD4(+) cells in wild-type mice protected from EAE, but not depletion of CD8(+) cells, although demyelination was reduced on removal of CD8(+) T cells. Immunization with immunodominant MOG(79-96) peptide led to EAE only in the presence of pertussis toxin (PT) in the inoculum. PT also triggered an earlier onset and more severe EAE in CD8(-/-) mice. We interpret our findings such that in an ontogenic lack of CD4(+) T cells, EAE is mediated by CD8(+) and elevated levels of alphabetaCD4(-)CD8(-) cells, and that CNS damage is partly enacted by the activity of CD8(+) T cells.
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PMID:Comparing the pathogenesis of experimental autoimmune encephalomyelitis in CD4-/- and CD8-/- DBA/1 mice defines qualitative roles of different T cell subsets. 1296 49

Experimental autoimmune encephalomyelitis was induced in macaques. T cell clones infiltrated into the brain lesion area were compared with those in blood. Intradermal immunization of macaques with brain white matter derived from healthy macaque in combination with pertussis toxin, induced neurological symptoms in two macaques. One died on day 25 after immunization, whereas the other survived. Gross examination of the brain from the dead macaque, showed clear hemorrhagic lesions in the white matter. Hematological analysis showed that drastic T cell response was induced in macaques immunized with white matter, but not in control macaques. Flow cytometric analysis of blood cells from the affected macaques demonstrated an increase of CD4 and CD8 T cell populations expressing the CD69 early activation marker. Single strand conformation polymorphism (SSCP) analysis of T cell receptor beta chain showed T cell clones infiltrated into the brain lesion, which were different from those found in the peripheral blood of the same monkey. The present paper shows that SSCP analysis of TCR is useful in studying clonality of T cells infiltrating into the brain tissue of macaque with EAE.
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PMID:Experimental autoimmune encephalomyelitis in cynomolgus monkeys. 1461 8


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