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J Vingerhoets

Publications and source records attributed to J Vingerhoets.

17 recordsLinked to original sources
PubMed2001

Longitudinal comparison of virus load parameters and CD8 T-cell suppressive capacity in two SIVcpz-infected chimpanzees.

In a longitudinal study we address the hypothesis that resis tance to disease progression in lentivirus-infected chimpanzees is related to potent non-cytotoxic suppression of virus replication. In a long-term follow-up, the viral suppressive capacity in two simian immunodeficiency virus (SIV)cpz-infected chimpanzees was correlated with two polymerase chain reaction (PCR)- and two culture-based virus load measurements. In both animals, quantitative virus isolation (QVI) tended to decline slowly, whereas in vitro virus suppression was sustained or increased over time. In general, plasma virus loads in SIVcpz-infected animals were maintained for extended periods of time. Based on current assays that measure virus suppressive capacity in peripheral blood, it was not possible to conclude that virus suppression played a major role in the maintenance of the disease-free state in lentivirus-infected chimpanzees.

Animals↗
PubMed2000

Despite high concordance, distinct mutational and phenotypic drug resistance profiles in human immunodeficiency virus type 1 RNA are observed in gastrointestinal mucosal biopsy specimens and peripheral blood mononuclear cells compared with plasma.

The gastrointestinal mucosa is a major lymphoid tissue reservoir for human immunodeficiency virus (HIV) replication. Genotypic and phenotypic resistance patterns of HIV type 1 (HIV-1) RNA isolated from colonic mucosa were compared with those from the plasma and peripheral blood mononuclear cells (PBMC) of 7 patients. Genotyping was performed using full-sequence analysis, and phenotyping was performed using a recombinant virus assay. Mutations in the reverse-transcriptase (kappa=.84) and protease (kappa=.73) genes were highly concordant among compartments. Similarly, phenotypic resistance patterns were highly concordant among compartments (intraclass correlation coefficient,.91). In 5 instances among 3 patients, a different genotypic result was observed between plasma and the other tissue compartments. Mixtures of wild-type and mutated HIV-1 RNA were present in the mucosa and PBMC but not in the plasma. Despite significant concordance among compartments, mucosal- and PBMC-derived viral RNA showed instances of discordance with plasma-derived virus that may suggest compartmentalization of virus.

Adult↗
PubMed2000

Prevalence of genotypic and phenotypic resistance to anti-retroviral drugs in a cohort of therapy-naïve HIV-1 infected US military personnel.

OBJECTIVE: While transmission of drug-resistant HIV-1 has been reported, estimates of prevalence of resistance in drug-naïve populations are incomplete. We investigated the prevalence of genotypic mutations and phenotypic antiretroviral resistance in a cohort of HIV-1 infected U.S. military personnel prior to the institution of antiretroviral therapy. DESIGN: Cross-sectional cohort study. METHODS: Plasma was obtained from 114 recently HIV-1 infected subjects enrolled in an epidemiological study. Genotypic resistance was determined by consensus sequencing of a PCR product from the HIV-1 pol gene. Sequences were interpreted by a phenotypic-genotypic correlative database. Resistance phenotypes were determined by a recombinant virus cell culture assay. RESULTS: Genotypic mutations and phenotypic resistance were found at a higher than expected frequency. Resistance to non-nucleoside reverse transcriptase inhibitors was most common, with a prevalence of 15% of 95 subjects by genotype and 26% of 91 subjects by phenotype. Genotypic and phenotypic resistance respectively were found in 4% and 8% of subjects for nucleoside reverse transcriptase inhibitors and in 10% and 1% for protease inhibitors. One subject harbored virus with resistance to all three drug classes. CONCLUSIONS: A substantial frequency of resistance to antiretroviral drugs was identified in a therapy-naïve U.S. cohort. In most cases, the genotypic and phenotypic assays yielded similar results, although the genotypic assay could detect some protease inhibitor resistance-associated mutations in the absence of phenotypic resistance. These data suggest the need for optimization of treatment guidelines based on current estimates of the prevalence of drug resistance in HIV-1 seroconverters.

Adult↗
PubMed1998

Altered receptor expression and decreased sensitivity of T-cells to the stimulatory cytokines IL-2, IL-7 and IL-12 in HIV infection.

A dysregulated production of regulatory cytokines has been proposed as a determinant in the progression of HIV infection. The sensitivity of T-cells to these cytokines has, however, not fully been investigated. Therefore, the responses of PBMC and T-cell subsets to the stimulatory cytokines IL-2, IL-7 and IL-12 in HIV-infected patients and HIV-negative controls were compared by examining their effect on the production of secondary cytokines (IFNgamma, IL-4 and IL-10), by simultaneous determination of T-cell activation and apoptosis and by measuring cytokine receptor expression. Production of IFNgamma was decreased in PBMC from the patients after stimulation with several combinations of stimulatory cytokines. IL-10 was only induced upon stimulation with IL-2 and IL-12 and tended to be produced more in patients. Expression of the different cytokine receptor chains showed complex alterations in HIV+ patients as compared to controls. The most pronounced changes were decreased expression of both IL-2Ralpha and IL-7Ralpha chain on CD8+ T-cells and an increase of IL-12Rbeta on both T-cell subsets from the patients. Evaluation of CD25 upregulation and blast formation revealed a deficient response to all three stimulatory cytokines in CD8+ but not in CD4+ T-cells from patients as compared to controls. Both CD4+ and CD8+ T-cells from the patients were less sensitive to the anti-apoptotic effect of IL-7 whereas only CD8+ T-cells were less sensitive to the anti-apoptotic effect of IL-2. The present data show that CD8+ T-cells, and to a lesser extent CD4+ T-cells, become less sensitive to IL-2, IL-7 and IL-12 during HIV infection. The decreased capacity of T-cells to respond to these cytokines could contribute to the HIV-related immune dysfunction.

Adult↗
PubMed1998

HBV-specific lymphoproliferative and cytokine responses in patients with chronic hepatitis B.

BACKGROUND/AIMS: Hepatitis B virus specific T cell responses are crucial for viral elimination but their nature is not fully understood. METHODS: We studied the regulation of proliferation and cytokine production after antigenic stimulation in peripheral blood mononuclear cells from chronically HBV-infected patients and subjects with natural immunity after recovery from an acute infection. Proliferation and production of interferon-gamma, IL-10 and tumor necrosis factor-alpha were determined after stimulation with HBcAg, HBeAg or HBsAg in the absence or presence of IL-12 or neutralizing antibodies to IL-12, interferon-gamma, IL-4, IL-10 or tumor necrosis factor-alpha. RESULTS: Upon stimulation with HBcAg or HBeAg, peripheral blood mononuclear cells from chronic hepatitis B virus patients displayed a clear class-II restricted proliferative response (SI greater than 2.5). Both interferon-gamma (less than 50 IU/ml) and IL-10 levels up to 600 pg/ml were detected. Proliferative or cytokine responses to HBsAg were very weak or absent. Addition of IL-12 to HBeAg-stimulated cultures increased the production of interferon-gamma to more than 200 IU/ml in all patients and slightly increased the production of IL-10. Neutralization of IL-10 increased the HBeAg-induced interferon-gamma production but had no effect on tumor necrosis factor-alpha production. Addition of anti-IL-4 or anti-tumor necrosis factor-alpha had no significant influence on proliferation or cytokine release. Importantly, in both chronic hepatitis B virus patients and naturally immune subjects, IL-12 induced proliferative and interferon-gamma responses in peripheral blood mononuclear cells stimulated with HBsAg. CONCLUSIONS: Our data indicate that peripheral blood mononuclear cells from chronic hepatitis B virus patients proliferate and produce interferon-gamma and IL-10 upon HBeAg but not upon HBsAg stimulation. IL-12 augments the HBeAg-induced responses and, additionally, provokes proliferation and interferon-gamma production in HBsAg-stimulated cultures.

Cryopreservation↗
PubMed1998

Superantigen activation of CD4+ and CD8+T cells from HIV-infected subjects: role of costimulatory molecules and antigen-presenting cells (APC)

T cell receptor (TCR) triggering via superantigens induces decreased proliferative responses and increased apoptosis in T cells from HIV-infected patients compared with controls. Our aim was to delineate the role of intrinsic T cell defects, of APC dysfunction and of cytokines and costimulatory signal dysregulation in the deficient responses of CD4+ and CD8+ T cells from HIV+ subjects to the superantigen Staphylococcus enterotoxin A (SEA). Proliferation and IL-2R alpha up-regulation on SEA-stimulated CD4+ and CD8+ T cells in whole blood were reduced in HIV+ subjects with CD4 counts < 500, compared with controls. Neither addition of IL-2, IL-12 or phorbol myristate acetate (PMA) nor neutralization of endogenous IL-10, tumour necrosis factor-alpha (TNF-alpha), TNF-beta or transforming growth factor-beta (TGF-beta) could restore the decreased activation by SEA. Possible intrinsic T cell defects were studied by presenting SEA on HLA-DR-transfected Chinese hamster ovary (CHO) cells, co-expressing LFA3 and/or CD80, to purified T cells. In this system CD8+ T cells from most HIV+ patients were hyporesponsive with regard to IL-2 production, IL-2R alpha up-regulation and proliferation, whereas clearly reduced responses were only shown in CD4+ T cells from AIDS patients. Similarly, apoptosis was increased in CD8+ T cells from all patients, but only in CD4+ T cells from AIDS patients. During HIV infection, the responses to TCR triggering through SEA are deficient in both T cell subsets. The intrinsic defect appears earlier during disease progression in purified CD8+ T than in CD4+ T cells, it occurs in conjunction with both CD2 and CD28 costimulation, and it is correlated with increased levels of apoptosis.

Animals↗
PubMed1997

CD8+ cells and not CD4+ T cells are hyporesponsive to CD28- and CD40L-mediated activation in HIV-infected subjects.

T cell dysfunction in HIV-infected subjects could be the consequence of altered sensitivity of CD4+ or CD8+ T cells to various costimulatory signals. Therefore, we studied proliferation and cytokine production in highly purified CD8+ and CD4+ T cells from HIV-infected and HIV- subjects, induced by co-activation via cell-bound CD80, CD86 and CD40 or by allo-activation. Regardless of the nature of the first and the costimulatory signal, CD8+ T cells from patients proliferated consistently less than controls, while responses from CD4+ T cells were similar in patients and controls. This phenomenon was observed after ligation of CD28 combined with anti-CD3 or phorbol myristate acetate (PMA), but also after allogeneic stimulation and after activation by CD40 and anti-CD3. Anti-CD3 combined with CD80 or CD86 induced a mixed Th1/Th2-type cytokine profile in both CD4+ and CD8+ T cells from controls, whereas anti-CD3 plus CD40 induced only low levels of Th2-type cytokines and no interferon-gamma (IFN-gamma) in CD4+ T cells. Compared with controls, CD4+ T cells from patients produced slightly lower levels of IL-10 but equal amounts of IFN-gamma, IL-4 and IL-5, while CD8+ T cells from patients produced less of all cytokines tested. In conclusion, responses of purified CD4+ T cells from HIV+ subjects to various costimulatory pathways are relatively intact, whereas CD8+ T cells are hyporesponsive at the level of proliferation and cytokine production. A generalized intrinsic CD8+ T cell failure might contribute to viral and neoplastic complications of HIV infection.

Adult↗
PubMed1997

Virologic, immunologic, and clinical follow-up of a couple infected by the human immunodeficiency virus type one, group O.

The pathogenic course (virologic, immunologic, and clinical changes) of infection due to human immunodeficiency virus type one (HIV-1) group O viruses is unknown at present. To address this issue, serial HIV-1 isolates from a married couple (patients A and B) infected with a group O virus were analyzed to determine the temporal association between disease status and alterations in several parameters including plasma viral burden as measured by semiquantitative polymerase chain reaction, changes in CD4+ T cells, presence of neutralizing antibodies, and the ability to induce syncytia on the MT2 cells. For patient A who has been asymptomatic for at least 8 years, both the absence of syncytium-inducing (SI) variants and the presence of autologous and heterologous neutralizing antibodies correlated with a clinically healthier status. In contrast, a switch from NSI to SI variants was observed in patient B in 1990, followed by an expanded in vitro host range, increased viral burden, and a sharp decrease in CD4+ T cells 4 years later. Moreover, plasma obtained from this patient uniformly failed to neutralize both autologous and heterologous viruses. These observations in patient B correlated with a slightly unfavorable clinical status. Based on our preliminary results, it appears that the pathogenic course of infections due to group O viruses is similar to that reported previously for infections due to group M viruses.

Acquired Immunodeficiency Syndrome↗
PubMed1995

A convenient and economical freezing procedure for mononuclear cells.

Cryopreservation techniques have become essential in longitudinal evaluation of lymphocyte function. This study describes a convenient method for freezing of peripheral blood mononuclear cells, using a small cryocontainer. Analysis of cell function, assayed by lymphoproliferation to recall antigens and by cytotoxic capacity of activated lymphocytes, was performed in parallel on fresh and frozen-thawed cells. Although cryopreservation did affect lymphocyte function, our results indicate that this freezing method performed equally well compared to a computer controlled device. We conclude that the cryocontainer has proved to be a suitable and practical tool in clinical studies and is an economical alternative to conventional methods.

Cell Division↗
PubMed1995

Phenotypic and functional parameters of cellular immunity in a chimpanzee with a naturally acquired simian immunodeficiency virus infection.

The cellular immunologic and virologic status of a chimpanzee, naturally infected with a human immunodeficiency virus type 1 (HIV-1)-like lentivirus (SIVcpz-ant), was compared longitudinally with those of 3 HIV-1-infected and 5 uninfected chimpanzees for a period of 49 months. Evidence of immune deficiency was not observed in the HIV-1-infected chimpanzees, nor could virus be isolated from plasma. Virus could be isolated from plasma of the SIVcpz-ant-infected chimpanzee, but clinical signs of immune deficiency were never observed. Absolute CD4+ cell counts remained relatively stable, but NK cells fluctuated significantly over time and tended to correlate inversely with the virus titer in peripheral blood. Although only CD8+ T cells were directly demonstrated to exert a suppressive effect on viral replication in vitro, the observed fluctuation of NK cells suggests that these cells may also be involved in the interaction with lentivirus infection in this species.

Animals↗
PubMed1995

In vitro stimulation of peripheral blood mononuclear cells (PBMC) from HIV- and HIV+ chancroid patients by Haemophilus ducreyi antigens.

The cellular immune responses to fractionated Haemophilus ducreyi antigens, coated on latex beads, were assessed in patients with chancroid and in controls, using an in vitro lymphocyte proliferation assay. Several fractions of H. ducreyi antigen revealed stimulating activity. However, only the molecular size ranges 91-78 kD, 59-29 kD, and 25-21 kD induced proliferation that may be specifically related to H. ducreyi infection. Lymphocytes from four HIV- patients, successfully treated for chancroid, were not stimulated by H. ducreyi antigen. In general, lymphocytes from HIV+ chancroid patients were less responsive to H. ducreyi antigen compared with those from HIV- chancroid patients. However, two HIV-infected patients showed exceptionally strong responses to high molecular weight fractions. To our knowledge this is the first report demonstrating that H. ducreyi contains specific T cell-stimulating antigens. Based on this work, further identification and purification of the T cell antigens is feasible.

Antigens, Bacterial↗
PubMed1995

Non-response to a recombinant pre-S2-containing hepatitis B vaccine: association with the HLA-system.

In this study, the immunogenicity of a recombinant pre-S2 containing hepatitis B vaccine was determined in a cohort of 147 homosexual men. Both seroconversion rate and geometric mean titers indicated that pre-S2 was less immunogenic than HBsAg. Forty-eight subjects, including nine non-responders and seven high-responders to HBsAg, were tested for HLA Class I and II antigens to study a possible association between HLA-type and non-response. Both HLA-B8 and HLA-DR3 were clearly overrepresented in non-responders to HBsAg. Non-response to pre-S2, observed in 7/9 non responders and 6/39 responders to HBsAg, was not associated with any of the tested HLA markers.

Adult↗
PubMed1994

The interleukin-2 receptor subunit expression and function on peripheral blood lymphocytes from HIV-infected and control persons.

The expression of interleukin-2 receptor (IL2R) was studied on circulating lymphocytes from HIV-infected (HIV+) and control subjects, using chain-specific monoclonal antibodies and indirect immunofluorescence flow cytometry. The IL2R alpha chain expression was decreased on CD4 and CD8 T cells from HIV+ persons compared to controls. Conversely, beta chain expression was enhanced on both T cell subsets from the patients. IL2R-subunit levels were similar on natural killer cells from patients and controls. To evaluate the function of IL2R, we investigated to what extent IL2 could induce CD69, an early activation marker of lymphocytes. A dose-dependent increase of CD69 expression was observed on T and NK cells from all subjects. The upregulation of CD69 was similar on CD4 T and NK cells from patients and controls, but was more pronounced on CD8 T cells from HIV+ compared to HIV- subjects. Based on inhibition studies, both the alpha and the beta chain contributed to the IL-2-induced CD69 expression on CD4 T cells, pointing to involvement of the high-affinity receptor. The early activation of CD8 T cells and NK cells was mainly dependent on the intermediate-affinity receptor. We conclude that significant changes in IL2R alpha and beta chain expression on circulating T cells occur after HIV infection, but that early activation through IL2 is preserved or enhanced, even in advanced stages.

Adult↗
PubMed1994

Deficient T-cell responses in non-responders to hepatitis B vaccination: absence of TH1 cytokine production.

The inability to mount a protective level (> or = 10 IU/l) of hepatitis B surface antigen (HBsAg)-specific antibodies after vaccination is presumably the consequence of a defect in the cellular immune regulation. We compared the in vitro immune responses of peripheral blood mononuclear cells (PBMC) from high, intermediate and non-responders, after stimulation with recombinant HBsAg. The absence of a proliferative response in non-responders was not reversed by removal of CD8+ T cells, indicating that HBsAg-specific CD8+ T-cell-induced suppression was not the underlying cause of non-responsiveness. Non-responders did not produce cytokines after HBsAg stimulation. High responders displayed a typical Th1-like profile since their PBMC produced interleukin-2 (IL-2) and gamma-interferon (IFN gamma) and no detectable IL-4 or IL-5 upon stimulation with HBsAg.

Adult↗
PubMed1994

Expression patterns of Fc gamma receptors, HLA-DR and selected adhesion molecules on monocytes from normal and HIV-infected individuals.

The expression and co-expression profiles of functionally important monocyte surface markers were compared between control and HIV+ individuals using combined physical gating and dim CD4 expression to delineate the monocytes. The Fc gamma RII (CD32), the MHC class II antigen HLA-DR and the adhesion molecules CD11a (LFA-1 alpha), CD18 and CD54 (ICAM-1) showed an unimodal distribution. Of these markers, CD11a and HLA-DR were up-regulated in the HIV+ subjects compared with controls. The expression levels of the adhesion molecules correlated with each other in both patients and controls. The CD11b (CR3-alpha), CD14, Fc gamma RI, and Fc gamma RIII markers were bimodally distributed. Compared with controls, monocytes from seropositives contained fewer CD14bright+ cells, an equal proportion of Fc gamma RIbright+ cells, but twice as many Fc gamma RIII+ cells. The expression level of Fc gamma RI and CD11b within their brightly positive subset increased as CD4 T cells decreased. Both in patients and controls, co-expression of bright CD11b, CD14 and Fc gamma RI was shown, whereas the Fc gamma RIII+ cells were negative or dim positive for the former triad. We conclude that the expression of two Fc gamma R (I and III), of the adhesion molecules CD11a and CD11b and of HLA-DR showed particular alterations on monocytes from HIV+ subjects. The relationship of these phenotypic observations with altered cytokine profiles and altered monocyte function is discussed.

Antigens, CD↗
PubMed1993

Decreased expression of the memory marker CD26 on both CD4+ and CD8+ T lymphocytes of HIV-infected subjects.

Using a novel anti-CD26 (or anti-dipeptidyl peptidase IV) monoclonal antibody, we showed that the absolute numbers and the proportions of T4 and T8 cells expressing CD26 were significantly lower in HIV-infected persons than in controls. The absolute number of CD26+ T4 cells decreased according to disease progression, whereas the number of CD26+ T8 cells was low throughout all clinical stages. These trends were similar in CD26 dim and bright positive T-cell subsets. In both controls and HIV-positive subjects, the CD26 bright positive T cells were restricted to the CD45RO+ subset and preferentially co-expressed CD25 but largely lacked HLA-DR and CD38. Recall antigen-responsive cells from seronegative individuals were shown to co-express CD26 and CD45RO. The deficient CD26 expression on T8 cells from HIV-infected subjects could be normally upregulated after in vitro stimulation. In contrast to decreased T-cell-bound CD26, the enzymatic activity of plasma CD26/dipeptidyl peptidase IV was unchanged in HIV-infected patients compared with controls. We conclude that HIV infection leads to a deficient in vivo co-expression of CD26 bright and CD45RO on T cells. We speculate that this deficiency might play a part in the decrease of immunological memory during HIV infection.

ADP-ribosyl Cyclase↗