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Biomedical subjects

L Meyaard

Publications and source records attributed to L Meyaard.

34 records · Page 2Linked to original sources
PubMed1994

Changes in cytokine secretion patterns of CD4+ T-cell clones in human immunodeficiency virus infection.

In addition to the loss of CD4+ T cells in later stages of human immunodeficiency virus (HIV) infection, functional defects of Th cells can already be observed in early infection. Decreased interleukin (IL)-2 and interferon (IFN)-gamma production by CD4+ T cells and diminished delayed type hypersensitivity reactions are indicative for impaired Th1 responses. We studied the cytokine secretion patterns of T-cell clones (TCC) generated by mitogenic stimulation of CD4+ memory T cells. Compared with TCC from HIV-negative controls, TCC isolated from HIV-infected individuals consistently showed increased IL-4 production, often paralleled by increased IL-5 and decreased IFN-gamma production. This resulted in a decreased percentage of Th1 clones with an increase in Th0 clones. To rule out the influence of interindividual differences, we studied two individuals from whom cells were available before and after infection with HIV. Indeed, an increase in Th2 cytokine secretion was observed after HIV-infection. Loss of Th1 and enhanced Th2 responses might further curtail cellular responses resulting in deficiency of cellular immunity in HIV infection.

CD4-Positive T-Lymphocytes↗
PubMed1994

Viro-immunological studies in acute HIV-1 infection.

OBJECTIVE: To monitor a patient who presented with symptomatic HIV-1 infection for virological and immunological parameters in relation to the clinical course. METHODS: Virological studies included determination of frequency of productively HIV-1-infected peripheral blood mononuclear cells (PBMC) and viral RNA load in plasma and p24 antigenaemia. Immunological studies included the analysis of T-cell subsets, the expression of activation markers, CD45RO and CD45RA antigens, the frequency of cells programmed for death, and T-cell function. RESULTS: During the first week post onset of primary HIV-1 infection symptoms high plasma titres of p24 and HIV-1 RNA were observed. The number of productively HIV-1-infected PBMC peaked, coinciding with CD4+ T lymphocytopaenia, during week 2 when clinical improvement started. CD8+ T lymphocytosis was observed 10 days post onset of clinical symptoms, the expanded cell population being of the CD8+CD38+, CD8+CD27+ and CD8+CD28- phenotype. CD8+ T lymphocytosis was paralleled by a high percentage of cells undergoing programmed cell death on in vitro culture. In vitro T-cell function was severely depressed during the first 10 days post onset of clinical symptoms. Within about 3 weeks, following resolution of clinical symptoms, phytohaemagglutinin-induced proliferation was restored to normal levels while responses to the CD3 monoclonal antibody only showed a partial restoration. During follow-up, concomitant with the rise of activated CD8+ T cells, p24 antigen levels and viral RNA load in serum as well as the number of HIV-producing PBMC steeply declined after 2 weeks. CONCLUSION: These findings demonstrate HIV-1-induced abnormalities during severe clinical symptoms of primary HIV-1 infection. The subsequent strong immune response, which is believed to be responsible for efficient control of viral replication, appears to precede clinical improvement.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Programmed death of T cells in human immunodeficiency virus infection. No correlation with progression to disease.

Programmed death of T cells has been proposed as one of the mechanisms by which HIV affects immune functions in stages of infection where the number of infected cells is low. Indeed, in HIV-infected individuals both CD4+ and CD8+ T cells are primed for programmed cell death, which can be enhanced by polyclonal stimulation. Here, we investigated programmed death of T cells in all stages of HIV infection, including acute infection. In individuals with primary infection the number of T cells dying due to apoptosis was much higher than in the asymptomatic phase of infection and paralleled increased numbers of CD8+ cells. In asymptomatic HIV-infected individuals, cells were dying in increased percentages compared with noninfected controls, although at much lower numbers than during acute infection. Death of T cells was not quantitatively correlated with CD4+ T cell numbers or appearance of more cytopathic, syncytium-inducing HIV variants. Analysis of the phenotype of cells undergoing apoptosis revealed that cell death was not confined to a specific T cell subset nor correlated with expression of certain T cell activation markers. Our results imply that the extent of programmed cell death of T cells in HIV infection does not correlate with progression to disease.

Antigen-Presenting Cells↗
PubMed1994

Quantitative analysis of CD4+ T cell function in the course of human immunodeficiency virus infection. Gradual decline of both naive and memory alloreactive T cells.

Early in human immunodeficiency virus (HIV) infection CD4+ and CD8+ T cells are qualitatively affected. Loss of responses to recall antigen precedes impaired responses to allogeneic MHC and mitogens. The selective quantitative loss of memory T cells in early infection, only partially explains the observed defects. We investigated whether functional loss of T cells is preferentially observed for memory T cells or whether both naive and memory T cell subsets are affected in the course of HIV infection. We studied the proliferative response of CD4+ T cells from HIV-infected individuals to alloantigens, to which normally both naive and memory T cells respond, by limiting dilution analysis. The decreased proliferative response to alloantigens in HIV-infected individuals was associated with a decreased precursor frequency of alloreactive cells. The frequency was decreased in both the CD45RA+ (naive) and the CD45RO+ (memory) subset of CD4+ T cells. Analysis of four individuals in the course of HIV infection revealed similar kinetics of the decline in function in both subsets. Although initially T cell defects may be accounted for by the selective quantitative loss of memory cells, in later stages of HIV infection the function of both CD45RA+ and CD45RO+ cells is affected.

CD3 Complex↗
PubMed1993

T-cell dysfunction in HIV infection: anergy due to defective antigen-presenting cell function?

Before CD4+ T cells are depleted, T cells in asymptomatic HIV-infected individuals are functionally abnormal. These T cells are programmed for death, are non-responsive and fail to produce interleukin-2 after antigenic stimulation. Our view is that these different T-cell abnormalities are explained by the effects of HIV on antigen-presenting cells. Alteration of the functions of the antigen-presenting cell may program T cells for activation-induced death, and may induce anergy in interleukin-2 and interferon-gamma secreting TH1 cells. This results in predominance of TH2 allergic responses instead of cellular immunity dependent on TH1 cells.

Animals↗
PubMed1993

Early replication steps but not cell type-specific signalling of the viral long terminal repeat determine HIV-1 monocytotropism.

The expression of human immunodeficiency virus type 1 (HIV-1) is enhanced after cell activation because of the interaction of cell-encoded nuclear factors that interact with binding sites in the long terminal repeats (LTRs). Here we studied the contribution of cell type-specific activation signals to differences in cytotropism of HIV-1 variants. Four closely related molecular HIV-1 clones with distinct biological phenotypes and different capacities to replicate in primary monocyte-derived macrophages (MDMs) or T cell lines were used. Sequence analysis of these LTRs revealed variation in functionally important regions. Adaptation of virus variants to particular host cells by differences in LTR responsiveness was analyzed. LTR-CAT constructs were transiently transfected in T cells that were stimulated with T cell-specific activation signals such as combinations of anti-CD3 or anti-CD28 MoAB or in primary monocytes that were stimulated with IL-3, IL-4, or GM-CSF. No differences in responsiveness to cell type-specific signals were demonstrated. To further elucidate the level of restriction in cell tropism, transfection of four full-length infectious molecular HIV-1 clones into 5-day cultured MDMs was performed. From all clones, competent virus could be rescued from MDMs by coculture with PHA-stimulated PBLs. However, following cell-free inoculation, proviral DNA could be detected by PCR analysis only in monocytes exposed to HIV-1 clones that previously were shown to establish productive infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1993

Lack of T cell dysfunction and programmed cell death in human immunodeficiency virus type 1-infected chimpanzees correlates with absence of monocytotropic variants.

In asymptomatic human immunodeficiency virus (HIV) infection in humans, disturbed T cell functions such as anergy and programmed cell death, thought to result from inappropriate signaling by antigen-presenting cells due to HIV infection, precede increase in virus load, decline in CD4+ T cell numbers, and subsequent disease progression. Here, in 3 long-term HIV-1-infected asymptomatic chimpanzees, antigen-presenting cell function was intact and T cells had normal proliferative capacity with no evidence of HIV-1-associated programmed cell death. Polymerase chain reaction analysis demonstrated low frequencies of cells harboring proviral DNA. Primary virus isolation from the infected animals demonstrated the absence of monocytotropic HIV-1 variants, in concordance with complete insusceptibility of chimpanzee monocytes for HIV-1 infection. Possibly, because of the incapacity of HIV-1 to infect monocytes, systemic immune dysfunction will not occur, contributing to controlled viral replication and maintenance of the asymptomatic state in HIV-infected chimpanzees.

Amino Acid Sequence↗
PubMed1992

Programmed death of T cells in HIV-1 infection.

In human immunodeficiency virus (HIV) infection, functional defects and deletion of antigen-reactive T cells are more frequent than can be explained by direct viral infection. On culturing, both CD4+ and CD8+ T cells from asymptomatic HIV-infected individuals died as a result of programmed cell death (apoptosis). Apoptosis was enhanced by activation with CD3 antibodies. Programmed cell death, associated with impaired T cell reactivity, may thus be responsible for the deletion of reactive T cells that contributes to HIV-induced immunodeficiency.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Effects of HIV-1 Tat protein on human T cell proliferation.

In inducing immunodeficiency in human immunodeficiency virus (HIV)-1 infection, a role for the HIV-1 Tat protein has been suggested. In addition to effects on viral transcription, the protein has been ascribed immunosuppressive functions, which were investigated in this study. Proliferation of purified T cells to CD3 monoclonal antibodies immobilized to plastic plates was inhibited up to 70% by addition of 5 micrograms/ml of the Tat protein. This inhibitory effect, however, was not observed in the presence of accessory cells. Furthermore, no effect of Tat protein could be observed on T cell proliferative responses to recall antigen which most likely is related to the presence of accessory cells in the cultures. Taken together, our results do not imply an important role for immunosuppressive effects of Tat in induction of immunodeficiency as observed in HIV infection in vivo.

Antigen-Presenting Cells↗