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J T van Dissel

Publications and source records attributed to J T van Dissel.

At least 55 records · Page 3Linked to original sources
PubMed2000

Detection of active tuberculosis infection by T cell responses to early-secreted antigenic target 6-kDa protein and culture filtrate protein 10.

The purified protein derivative (PPD) skin test has no predictive value for tuberculosis (TB) in Mycobacterium bovis bacillus Calmette-Guérin (BCG)-vaccinated individuals because of cross-reactive responses to nonspecific constituents of PPD. T cell responses to early-secreted antigenic target 6-kDa protein (ESAT-6) and the newly identified culture filtrate protein 10 (CFP-10), 2 proteins specifically expressed by M. tuberculosis (MTB) but not by BCG strains, were evaluated. Most TB patients responded to ESAT-6 (92%) or CFP-10 (89%). A minority of BCG-vaccinated individuals responded to both ESAT-6 and CFP-10, their history being consistent with latent infection with MTB in the presence of protective immunity. No responses were found in PPD-negative controls. The sensitivity and specificity of the assay were 84% and 100%, respectively, at a cutoff of 300 pg of interferon-gamma/mL. These data indicate that ESAT-6 and CFP-10 are promising antigens for highly specific immunodiagnosis of TB, even in BCG-vaccinated individuals.

Adolescent↗
PubMed2000

Human deficiencies in type 1 cytokine receptors reveal the essential role of type 1 cytokines in immunity to intracellular bacteria.

Studies on patients with idiopathic, severe infections due to poorly pathogenic mycobacteria and Salmonella have revealed that many of these patients are unable to produce or respond to interferon-gamma (IFN-gamma). This inability results from causative, deleterious genetic mutations in either one of four different genes in the type 1 cytokine cascade, encoding interleukin-12Rbeta1 (IL-12Rbeta1), IL-12p40, IFN-gammaR1 or IFN-gammaR2. The immunological phenotypes resulting from the seven groups of complete or partial deficiencies in type 1 cytokine (receptor) genes that have been distinguished thus far will be summarized and discussed, and placed in a broader context in relation to disease susceptibility.

Bacterial Infections↗
PubMed2000

Candidacidal activities of human lactoferrin peptides derived from the N terminus.

In light of the need for new antifungal agents, the candidacidal activities of human lactoferrin (hLF) and synthetic peptides representing the first, hLF(1-11), and second, hLF(21-31), cationic domains of its N terminus were compared. The results revealed that hLF(1-11) was more effective in killing fluconazole-resistant Candida albicans than hLF(21-31) and much more effective than lactoferrin, as determined microbiologically and by propidium iodide (PI) staining. By using hLF(1-11) and various derivatives, it was found that the second and third residues of the N terminus of hLF(1-11) were critical for its candidacidal activity. Detailed investigation to elucidate the mechanism of action of hLF(1-11) revealed a dose-dependent release of ATP by Candida upon exposure to hLF(1-11). Our observations that sodium azide reduced the PI uptake and candidacidal activity of hLF(1-11) and that, upon exposure to hLF(1-11), the fluorescent dye rhodamine 123 first accumulated inside the mitochondria and later was released into the cytoplasm indicate that the peptide triggers the energized mitochondrion. Furthermore, oxidized ATP, which interferes with the interaction of ATP with its extracellular receptors, blocked the candidacidal action of hLF(1-11), as measured microbiologically and by PI staining. Addition of ATP (or analogues) was not a sufficient stimulus to kill C. albicans or to act synergistically with suboptimal concentrations of the peptide. The main conclusions are that the first two arginines at the N terminus of hLF are critical in the candidacidal activity of hLF(1-11) and that extracellular ATP is essential but not sufficient for the peptide to exert its candidacidal activity.

Adenosine Triphosphate↗
PubMed2000

Antigenic equivalence of human T-cell responses to Mycobacterium tuberculosis-specific RD1-encoded protein antigens ESAT-6 and culture filtrate protein 10 and to mixtures of synthetic peptides.

The early secreted antigenic target 6-kDa protein (ESAT-6) and culture filtrate protein 10 (CFP-10) are promising antigens for reliable immunodiagnosis of tuberculosis. Both antigens are encoded by RD1, a genomic region present in all strains of Mycobacterium tuberculosis and M. bovis but lacking in all M. bovis bacillus Calmette-Guérin vaccine strains. Production and purification of recombinant antigens are laborious and costly, precluding rapid and large-scale testing. Aiming to develop alternative diagnostic reagents, we have investigated whether recombinant ESAT-6 (rESAT-6) and recombinant CFP-10 (rCFP-10) can be replaced with corresponding mixtures of overlapping peptides spanning the complete amino acid sequence of each antigen. Proliferation of M. tuberculosis-specific human T-cell lines in response to rESAT-6 and rCFP-10 and that in response to the corresponding peptide mixtures were almost completely correlated (r = 0.96, P < 0.0001 for ESAT-6; r = 0.98, P < 0.0001 for CFP-10). More importantly, the same was found when gamma interferon production by peripheral blood mononuclear cells in response to these stimuli was analyzed (r = 0.89, P < 0.0001 for ESAT-6; r = 0.89, P < 0.0001 for CFP-10). Whole protein antigens and the peptide mixtures resulted in identical sensitivity and specificity for detection of infection with M. tuberculosis. The peptides in each mixture contributing to the overall response varied between individuals with different HLA-DR types. Interestingly, responses to CFP-10 were significantly higher in the presence of HLA-DR15, which is the major subtype of DR2. These results show that mixtures of synthetic overlapping peptides have potency equivalent to that of whole ESAT-6 and CFP-10 for sensitive and specific detection of infection with M. tuberculosis, and peptides have the advantage of faster production at lower cost.

Antigens, Bacterial↗
PubMed1999

Antibodies against pneumococcal polysaccharides after vaccination in HIV-infected individuals: 5-year follow-up of antibody concentrations.

We studied the production of IgG antibodies against eight pneumococcal polysaccharide serotypes (PPS) 1, 4, 6B, 9V, 14, 18C, 19F and 23F after vaccination of 50 HIV-infected adults with 23-valent Pneumovax((R))23 and the course of the antibodies against four PPS during the following years. Mean antibody concentrations against PPS 18C, 19F and 23F were sigificantly lower in the patients with CD4(+)-lymphocyte counts <200x10(6)/l than in healthy controls; mean antibody concentrations against PPS 1, 4, 9V, 6B and 14 were similar in HIV-infected individuals and controls. Although it has been assumed that polysaccharides induce a T-cell-independent immune response, our results indicate that some PPS are T-cell-independent type 2 antigens. The rates of decline of mean antibody concentrations in HIV-infected individuals and in healthy controls were similar during 5 y after vaccination. However, as a consequence of the low postvaccination antibody concentrations against several PPS, within 3 y after vaccination most HIV-infected individuals had antibody concentrations below the level which is assumed to be required for protection.

Adult↗
PubMed1999

Impaired antibody response after immunization of HIV-infected individuals with the polysaccharide vaccine against Salmonella typhi (Typhim-Vi).

Infections with Salmonella species, including Salmonella typhi, are more frequently observed in HIV-infected individuals than in healthy individuals. HIV-infected individuals were vaccinated with polysaccharide vaccine against Salmonella typhi (Typhim-Vi) which is assumed to be a T-cell-independent antigen. We found that the antibody response in patients with < 200 x 10(6)/l CD4+ T lymphocytes was significantly lower compared with patients with > or = 200 x 10(6)/l CD4+ T lymphocytes and healthy controls. The antibody response after vaccination with the polysaccharide salmonella Vi-antigen was correlated with the number of CD4+ T lymphocytes and therefore Typhim-Vi can be considered to be a T-cell-independent type 2 antigen. The results of this study indicate that after vaccination the proportion of HIV-infected individuals with protective antibody concentrations against Salmonella typhi will be lower than in healthy controls.

Adult↗
PubMed1999

[Toxic shock-like syndrome caused by streptococci].

Since the mid-eighties an increase of severe infections with invasive group A streptococci (GAS) has been noticed throughout the world, not only in the elderly but in healthy adults as well. The acute presenting infection starts with fever, enanthema, generalised erythema, rapidly progressing into shock and multiorgan failure, and is called streptococcal toxic shock syndrome (STSS). Despite surgical and antibiotic therapy with penicillin and clindamycin the mortality is high. There are as yet insufficient data in patients with STSS to decide between penicillin en clindamycin. Intravenous administration of high dose gammaglobulin, advocated in the USA, might neutralize the exotoxins, but the effectiveness of this therapy has not been established yet.

Adult↗
PubMed1999

Antibiotic-induced cell wall fragments of Staphylococcus aureus increase endothelial chemokine secretion and adhesiveness for granulocytes.

Antibiotics release inflammatory fragments, such as lipoteichoic acid (LTA) and peptidoglycan (PG), from the cell wall of Staphylococcus aureus. In this study, we exposed S. aureus cultures to a number of beta-lactam antibiotics (imipenem, flucloxacillin, and cefamandole) and protein synthesis-inhibiting antibiotics (erythromycin, clindamycin, and gentamicin) and investigated whether supernatants of these cultures differ in their capacity to stimulate endothelial cells (EC). After 24 h of incubation, endothelial adhesiveness for leukocytes, surface expression of various adhesion molecules, and secretion of the chemokines interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) were measured. Supernatants of beta-lactam-exposed cultures (designated beta-lactam supernatants) enhanced the adhesiveness of EC for granulocytes, whereas those of protein synthesis-inhibiting antibiotic-exposed cultures (designated protein synthesis-inhibitor supernatants) did not. This hyperadhesiveness coincided with a higher intercellular adhesion molecule-1 expression on the surface of the stimulated EC. In addition, EC stimulated with beta-lactam supernatants secreted significantly higher concentrations of the chemokines IL-8 and MCP-1 than those stimulated with protein synthesis-inhibitor supernatants. The finding that the concentrations of LTA and PG in beta-lactam supernatants were much higher than those in protein synthesis-inhibitor supernatants suggests that the observed differences in stimulatory effect between these supernatants are a result of differences in the release of cell wall fragments, although the presence of other stimulatory factors in the supernatants cannot be excluded. In conclusion, our results argue for a release of LTA and PG from S. aureus after exposure to beta-lactam antibiotics that enhances the development of a systemic inflammatory response by stimulating EC such that adhesiveness for granulocytes is increased and large amounts of IL-8 and MCP-1 are secreted.

Anti-Bacterial Agents↗
PubMed1999

Immunoglobulin G (IgG) subclass distribution and IgG1 avidity of antibodies in human immunodeficiency virus-infected individuals after revaccination with tetanus toxoid.

In human immunodeficiency virus (HIV)-infected individuals the amount of antibodies formed after vaccination with T-cell-dependent recall antigens such as tetanus toxoid is proportional to the peripheral blood CD4(+) T-lymphocyte counts. To investigate whether the immunoglobulin G (IgG) subclass distribution and avidity of the antibodies produced after vaccination are affected as well, we gave 13 HIV-infected adults with low CD4(+) T-lymphocyte counts (<200 x 10(6)/liter; group I), 11 HIV-infected adults with intermediate CD4(+) T-lymphocyte counts (>/=200 x 10(6)/liter; group II), and 5 healthy controls booster immunizations with tetanus toxoid. The prevaccination antibody concentrations against tetanus toxoid were similar in the HIV-infected and healthy adults. After vaccination the total IgG and the IgG1 anti-tetanus toxoid antibody concentrations were significantly lower in group I than in group II and the controls. The avidity of the IgG1 anti-tetanus toxoid antibodies formed by HIV-infected adults was within the range for healthy controls, irrespective of their CD4(+) T-lymphocyte counts.

Adult↗
PubMed1999

Anti-CD14 monoclonal antibodies inhibit the production of tumor necrosis factor alpha and interleukin-10 by human monocytes stimulated with killed and live Haemophilus influenzae or Streptococcus pneumoniae organisms.

In previous studies, we have shown that intact, heat-killed, gram-negative bacteria (GNB) and gram-positive bacteria (GPB) can stimulate the production of various proinflammatory and anti-inflammatory cytokines. The objective of the present study was to investigate whether the production of tumor necrosis factor alpha (TNF) and interleukin-10 (IL-10) by human monocytes stimulated by intact heat-killed or live Haemophilus influenzae or Streptococcus pneumoniae is mediated by CD14. Two anti-CD14 monoclonal antibodies (MAbs) were used to study the interaction between human monocytes and bacteria; lipopolysaccharide (LPS) was used to validate the effect of anti-CD14 MAb. MAb 18E12 decreased significantly TNF and IL-10 production upon stimulation with LPS or heat-killed bacteria and TNF production during stimulation by live bacteria. MAb My-4 decreased production of TNF and IL-10 by monocytes stimulated with LPS, IL-10 but not TNF production upon stimulation with heat-killed H. influenzae, and production of neither TNF nor IL-10 upon stimulation with S. pneumoniae. Together, these results led to the conclusion that CD14 is involved in the recognition and stimulation of human monocytes by intact GNB and GPB. Consequentially, the option for adjunctive treatment of severe infections with anti-CD14 MAb is postulated.

Antibodies, Monoclonal↗
PubMed1998

Restored humoral immune response to influenza vaccination in HIV-infected adults treated with highly active antiretroviral therapy.

BACKGROUND: Highly active antiretroviral therapy (HAART) effectively suppresses replication of HIV and is accompanied by an increase in CD4+ T lymphocytes. Whether the increase in CD4+ T lymphocytes in the blood is a reflection of a reconstitution of the immune functions is unknown. We investigated the recovery of the humoral immune response during HAART after immunization with T-cell-dependent influenza vaccine. METHODS: Forty-one men and three women infected with HIV and treated with HAART, and 15 healthy hospital staff members were immunized with trivalent influenza subunit vaccine. Antibody titres were determined by haemagglutination inhibiting assay in sera obtained before and 30 days after immunization. Lymphocyte subsets were determined in blood samples taken at the time of vaccination. RESULTS: In all HIV-infected individuals, treatment with HAART caused a median reduction of 2.3 log10 in HIV-1 load. The median increase of CD4+ T lymphocytes after initiation of HAART was 170 x 10(6)/l. The antibody response to influenza antigens was proportional to the number of memory CD4+ T lymphocytes in the blood at the time of vaccination. When a group of patients and healthy controls with approximately similar CD4+ T-lymphocyte counts were considered, the antibody titres after vaccination for influenza strain H1N1 and influenza B did not differ between patients and controls (P=0.12). Vaccination of patients with a CD4+ T-lymphocyte count of < 200 x 10(6)/l (mean 85 x 10(6)/l) before the start of HAART and with a mean of 282 x 10(6)/l CD4+ T lymphocytes at the time of vaccination as a result of HAART, demonstrated a substantial antibody response whereas patients with a CD4+ T lymphocyte count of < 200 x 10(6)/l (mean 56 x 10(6)/l) not treated with HAART (historical controls), and vaccinated with a similar influenza vaccine, failed to induce an antibody response. CONCLUSION: The present findings demonstrate a recovery of the humoral immune response to influenza antigens in HIV-infected individuals treated with HAART. This indicates that functional improvement of antigen specific CD4+ T helper cell reponses occurs.

Adult↗
PubMed1998

Severe mycobacterial and Salmonella infections in interleukin-12 receptor-deficient patients.

Interleukin-12 (IL-12) is a cytokine that promotes cell-mediated immunity to intracellular pathogens by inducing type 1 helper T cell (TH1) responses and interferon-gamma (IFN-gamma) production. IL-12 binds to high-affinity beta1/beta2 heterodimeric IL-12 receptor (IL-12R) complexes on T cell and natural killer cells. Three unrelated individuals with severe, idiopathic mycobacterial and Salmonella infections were found to lack IL-12Rbeta1 chain expression. Their cells were deficient in IL-12R signaling and IFN-gamma production, and their remaining T cell responses were independent of endogenous IL-12. IL-12Rbeta1 sequence analysis revealed genetic mutations that resulted in premature stop codons in the extracellular domain. The lack of IL-12Rbeta1 expression results in a human immunodeficiency and shows the essential role of IL-12 in resistance to infections due to intracellular bacteria.

Adult↗
PubMed1998

Anti-inflammatory cytokine profile and mortality in febrile patients.

BACKGROUND: An anti-inflammatory cytokine profile on whole-blood stimulation in vitro is associated with fatal outcome of meningococcal disease. We investigated whether an anti-inflammatory cytokine profile in the circulation is associated with adverse outcome in other infectious diseases. METHODS: We enrolled 464 consecutive patients (272 men, 192 women) who presented to hospital with fever (> or = 38.2 degrees C). On admission we measured plasma interleukin 10 (IL-10) and tumour necrosis factor alpha (TNF alpha), and collected clinical and microbiological data on the febrile illness, then followed up all patients for clinical outcome. FINDINGS: In at least 399 of the 464 patients fever was caused by infection. 33 patients died after a median hospital stay of 11 days (interquartile range 3-20). Concentrations of IL-10 were significantly higher in non-survivors (median 169 pg/mL [IQR 83-530]) than in survivors (median 88 pg/mL [42-235], p=0.042). When dichotomised around the median, the mortality risk was two times higher in patients who had high concentrations of IL-10 than in those with low concentrations (relative risk 2.39 [95% CI 1.07-5.33]), in patients with low and high concentrations of TNF alpha. In the 406 patients without haemodynamic deterioration in the first 24 h, IL-10 was higher and TNF alpha lower in patients who died than in those who survived. The ratio of IL-10 to TNF alpha was higher in non-survivors (median 6.9 [3.0-21.0]) than in survivors (median 3.9 [2.0-7.0], p=0.040). This ratio was highest in patients who died without underlying disease (median 21.5 [5.0-25.0]). Age, sex, and duration of fever before admission did not explain the differences in IL-10 and TNF alpha. INTERPRETATION: An anti-inflammatory cytokine profile of a high ratio of IL-10 to TNF alpha is associated with fatal outcome in febrile patients with community-acquired infection. Our findings caution against a widespread use of proinflammatory cytokine inhibition in patients with sepsis.

Adolescent↗