Biomedical subjects

Tao Dong

Publications and source records attributed to Tao Dong.

30 records · Page 2Linked to original sources

PubMed2004

Screening for HIV-specific T-cell responses using overlapping 15-mer peptide pools or optimized epitopes.

The IFN-y enzyme-linked immunospot (ELI-Spot) assay is often used to map HIV-specific CD8 T-cell responses. We compared overlapping 15-mer pools with optimized CD8 epitopes to screen ELISpot responses in HIV-infected individuals. The 15-mer pools detected responses to previously undefined epitopes, but often missed low-level responses to predefined epitopes, particularly when the epitope was central in the 15-mer, rather than at the N-terminus or C-terminus. These factors should be considered in the monitoring of HIV vaccine trials.

CD8-Positive T-Lymphocytes↗

PubMed2004

Immune activation and CD8+ T-cell differentiation towards senescence in HIV-1 infection.

Progress in the fight against the HIV/AIDS epidemic is hindered by our failure to elucidate the precise reasons for the onset of immunodeficiency in HIV-1 infection. Increasing evidence suggests that elevated immune activation is associated with poor outcome in HIV-1 pathogenesis. However, the basis of this association remains unclear. Through ex vivo analysis of virus-specific CD8(+) T-cells and the use of an in vitro model of naïve CD8(+) T-cell priming, we show that the activation level and the differentiation state of T-cells are closely related. Acute HIV-1 infection induces massive activation of CD8(+) T-cells, affecting many cell populations, not only those specific for HIV-1, which results in further differentiation of these cells. HIV disease progression correlates with increased proportions of highly differentiated CD8(+) T-cells, which exhibit characteristics of replicative senescence and probably indicate a decline in T-cell competence of the infected person. The differentiation of CD8(+) and CD4(+) T-cells towards a state of replicative senescence is a natural process. It can be driven by excessive levels of immune stimulation. This may be part of the mechanism through which HIV-1-mediated immune activation exhausts the capacity of the immune system.

Aging↗

PubMed2004

Recognition of HLA-A3 and HLA-A11 by KIR3DL2 is peptide-specific.

The recognition of MHC class I molecules by killer cell immunoglobulin-like receptors (KIR) is central to the control of NK cell function and can also modulate the CTL activation threshold. Among KIR receptors, KIR3DL2 is thought to interact with HLA-A3 and -A11, although direct evidence has been lacking. In this study, we show that HLA-A3 and -A11 tetramers specifically bind to KIR3DL2*001 transfectants and that this recognition is peptide-specific. Single amino acid substitutions in the nonamer peptide underline a critical role for residue 8 in recognition of KIR3DL2. However, the role of this interaction in vivo still remains to be established.

Flow Cytometry↗

PubMed2004

[Studies on the chemical constituents from culbs of hybridized Bulbus Fritillariae Ussuriensis].

OBJECTIVE: To study the chemical constituents of hybridized Bulbus Fritillariae Ussuriensis. METHOD: The chemical constituents were isolated by silica column chromatography and their structures were identified by physical and chemical eveidences and spectral analysis (IR, 1H-NMR, 13C-NMR, 2D-NMR, MS). RESULT: Seven compounds were obtained and identified as (20S,25S)5alpha, 14alpha, 17beta-cevanine-6beta-hydroxy-3-one (hupehenirine, ZF1), (20S,25S)5alpha, 14alpha, 17beta-cevanine-3beta-hydroxy-6-one (hupehenizine, ZF2), (20R,25S)5alpha, 14alpha-cevanine-3beta,20beta-dihydroxy-6-one (peiminine, verticinone, ZF3), (20S,25S)5alpha, 14alpha, 17beta-cevanine-3beta, 6beta-dihydroxy (hupehenine, ZF4), (20R,25S)5alpha, 14alpha-cevanine-3beta, 6beta, 20beta-trihydroxy (isoverticine, ZF5), (20R,25S)5alpha, 14alpha-cevanine-3beta, 6alpha, 20beta-trihydroxy (peimine, verticine, ZF6), (20S,25S)5alpha, 14alpha, 17beta-evanine-6beta-hydroxy-3beta-O-beta-D-glucoside (hupeheninoside, ZF7). CONCLUSION: Compounds ZF1-7 were isolated from hybridized Bulbus Fritillariae Ussuriensis for the first time.

Cevanes↗

PubMed2003

The T cell surface--how well do we know it?

The overall degree of complexity of the T cell surface has been unclear, constraining our understanding of its biology. Using global gene expression analysis, we show that 111 of 374 genes encoding well-characterized leukocyte surface antigens are expressed by a resting cytotoxic T cell. Unexpectedly, of 97 stringently defined, T cell-specific transcripts with unknown functions that we identify, none encode proteins with the modular architecture characteristic of 80% of leukocyte surface antigens. Only two encode proteins with membrane topologies found exclusively in cell surface molecules. Our analysis indicates that the cell type-specific composition of the resting CD8+ T cell surface is now largely defined, providing an insight into the overall compositional complexity of the mammalian cell surface and a framework for formulating systematic models of T cell surface-dependent processes, such as T cell receptor triggering.

Antigens, Surface↗

PubMed2003

Original antigenic sin and apoptosis in the pathogenesis of dengue hemorrhagic fever.

Dengue virus presents a growing threat to public health in the developing world. Four major serotypes of dengue virus have been characterized, and epidemiological evidence shows that dengue hemorrhagic fever (DHF), the more serious manifestation of the disease, occurs more frequently upon reinfection with a second serotype. We have studied dengue virus-specific T-cell responses in Thai children. During acute infection, few dengue-responsive CD8+ T cells were recovered; most of those present showed an activated phenotype and were undergoing programmed cell death. Many dengue-specific T cells were of low affinity for the infecting virus and showed higher affinity for other, probably previously encountered strains. Profound T-cell activation and death may contribute to the systemic disturbances leading to DHF, and original antigenic sin in the T-cell responses may suppress or delay viral elimination, leading to higher viral loads and increased immunopathology.

Apoptosis↗

PubMed2003

Effects of fish oil on lymphocyte proliferation, cytokine production and intracellular signalling in weanling pigs.

It has been widely documented that fish oil attenuates inflammatory responses partially via down-regulation of T-lymphocyte function. To determine the anti-inflammatory role of fish oil in weanling pigs, we investigated the effects of fish oil and its functional constituents on peripheral blood lymphocyte proliferation, cytokine production and subsequent intracellular signalling in inflammatory-challenged weanling pig and in in vitro cultured lymphocytes. Fish oil (7%) or corn oil (7%) was supplemented to 72 crossbred pig (7.6 +/- 0.3 kg BW and 28 +/- 3 days of age) in a 2 x 2 factorial experiment that included an Eacherichia coil lipopolysaccharide (LPS) challenge (challenged or not challenged). On day 14 and 28 of the experiment, 200 microg/kg BW of LPS or an equivalent amount of sterile saline was administered to the pigs by intraperitoneal injection. Blood samples were collected on days 15 and 29 to determine peripheral blood lymphocyte proliferation, interleukin-1beta (IL-1beta) and interleukin-2 (IL-2) production. The results showed that inflammatory challenge decreased average daily gain (P < 0.05) and average daily feed intake (P < 0.05) during days 15-28. Fish oil supplementation had no effect on growth performance. Inflammatory challenge increased lymphocyte proliferative response to concanavalin A (Con A) (P < 0.05) following each challenge. Fish oil tended to suppress (P < 0.1) the proliferation following the first challenge. Similarly, fish oil tended to reduce IL-1beta production (P < 0.1) following the second challenge and IL-2 (P < 0.1) production following the first challenge in both challenged and unchallenged pigs compared with corn oil. In parallel in vitro experiments, peripheral blood lymphocytes of weanling pigs were incubated with various concentrations of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) or linoleic acid (LA) (0, 20, 40, 60, 80, 100 microg/ml). EPA, DHA and high levels of LA predominantly suppressed IL-1beta (P < 0.05), IL-2 (P < 0.05) production and subsequent lymphocyte proliferation (P < 0.05). Low levels of LA increased (P < 0.05) IL-2 production. Compared with LA, EPA resulted in a stronger inhibition of lymphocyte proliferation (P < 0.05) and IL-2 (P < 0.01), and DHA resulted in a stronger inhibition of IL-1beta (P < 0.05) and IL-2 (P < 0.01). To elucidate the mechanism(s) by which fish oil and its functional constituents suppressed lymphocyte function, the kinetics of intracellular [Ca2+]i and protein kinase C activity were determined in in vitro experiments. EPA, DHA and LA exerted very similar dose-dependent stimulatory effects on intracellular Ca2+. EPA and DHA inhibited protein kinase C activity (P < 0.05), while LA had no significant effect (P > 0.05). These results suggest that fish oil and its functional constituents (EPA and DHA) exerted an anti-inflammatory effect by down-regulation of lymphocyte activation in weanling pigs, possibly by manipulation of intracellular signalling.

Animals↗

PubMed2003

Effects of dietary vitamin K levels on bone quality in broilers.

This study was conducted to evaluate the effects of dietary vitamin K (menadione) on bone quality in cage-raised broilers. Three hundred and sixty male broilers were randomly allotted to one of six treatments, with six replicate pens per treatment and 10 chicks per pen. Broilers were fed one of six diets including a control diet or the control diet plus graded levels of vitamin K (0.5 mg/kg, 2 mg/kg, 8 mg/kg, 32 mg/kg and 128 mg/kg). Water and feed were provided ad libitum during the 7-week experimental period. Results indicated that vitamin K supplementation of broilers diets significantly effected bone quality and feed efficiency. The treatment containing vitamin K at 8 mg/kg improved growth performance (during weeks 6-7) and bone quality (during weeks 0-3). In our study, hydroxyapatite binding capacity of serum osteocalcin (during weeks 0-3), bone breaking strength, bone flexibility, bone ash weight increased linearly (P < 0.05) and bone mineral density, bone mineral content increased quadratically (P < 0.05) with increasing supplementation of vitamin K. In conclusion, to gain optimum bone quality and broiler performance, our studies suggest that the concentration of vitamin K in broilers diets should be 8 mg/kg, 2 mg/kg, and 2 mg/kg, for the starter, grower and finisher phases, respectively. Furthermore, it was shown that the starter period is an important phase for improving bone quality. In addition, this study validated the mechanism of vitamin K effects on bone quality. Vitamin K boosts the carboxylation of osteocalcin and decreases the concentration of serum under-carboxylated osteocalcin enhancing hydroxyapatite binding capacity of serum osteocalcin and improving bone quality.

Animal Feed↗

PubMed2002

HIV-1-specific CD8 T cell responses in a pediatric slow progressor infected as a premature neonate.

We describe the long-term survival of an individual infected with HIV-1 during extrauterine life as a premature newborn. In the absence of viral attenuation in the Nef/LTR structure or significant co-receptor polymorphisms, slow progression was associated with the strong HIV-1-specific broadly cross-reactive CD8 T cell responses. HIV-1 infection as early as 25 weeks' gestation may thus results in the development of immune responses that control viral replication and lead to prolonged survival.

Adolescent↗

PubMed2002

HLA typing in a Kenyan cohort identifies novel class I alleles that restrict cytotoxic T-cell responses to local HIV-1 clades.

OBJECTIVES: To investigate HLA class I allele frequencies in a Kenyan commercial sex worker (CSW) cohort, and to examine HIV-1 specific cytotoxic T lymphocyte (CTL) responses directed against epitopes derived from locally prevalent clade A virus. METHODS: PCR-single strand polymorphism HLA class I typing. Sequencing of novel alleles and examination of their distribution in the CSW cohort, and a low risk HIV uninfected cohort. The peptide-binding motif of a novel class I allele was predicted, and a panel of candidate CTL epitopes was synthesized whose functional significance was examined using ELISpot and Cr release assays. RESULTS: Class I HLA-A and B frequencies within the cohort are presented. Two novel class I alleles were found, HLA-B*4415 and HLA-Cw*0407. These two class I alleles were relatively common, both in the CSW cohort (2.1% and 3.3% respectively) and in a cohort of lower risk women (1.9% and 3.8% respectively). Allele HLA-B*4415 restricted CTL responses against a novel epitope (EEKAFSPEV) derived from p24 of clade A HIV-1, and HLA-Cw0407 restricted CTL against a predefined HLA-Cw*0401 gp120 epitope. CONCLUSIONS: Multi-epitope vaccine design requires knowledge of HLA class I distribution and HIV CTL epitope characterization in potential target populations. The description of two novel HLA class I alleles at high frequency in this high risk Kenyan CSW cohort suggests that HLA mapping of vaccine cohorts and subsequent characterization of local CTL epitopes will be warranted prior to vaccine trials.

Cohort Studies↗

PubMed2002

Cross-reactive cytotoxic T lymphocytes against a HIV-1 p24 epitope in slow progressors with B*57.

OBJECTIVES: To determine whether CD8 T lymphocytes from HIV-1-infected patients expressing B*5701 and B*5703 show broad cross-reactivity against different variants of a conserved p24 epitope, which might account for the good prognosis of HIV-1-infected individuals with HLA-B*57. DESIGN: B*5701+ and B*5703+ were recruited from Nairobi, Kenya and from Oxford, UK. All patients had been HIV positive for at least 8 years and could be categorized as slow progressors. METHODS: CD8 cytotoxic T cell clones were generated from B*5701+ and B*5703+ donors and tested for their ability to recognize clade variants of an index p24 epitope in standard cytolytic assays. Cross-reactive responses in freshly isolated peripheral blood mononuclear cells (PBMC) were assessed by interferon-gamma (IFNgamma) production and tetramer binding. RESULTS: Broad cross-clade reactivity for both cytolysis and tetramer binding was observed in CD8 T cell clones from patients harbouring the index epitope sequence. Patterns of cross-reactivity were similar in freshly isolated PBMC but varied between individuals in terms of strength and breath of responses generated. One common variant induced an unusual response with tetramer binding but often failed to induce IFNgamma production, and another was a weak stimulator of both IFNgamma and cytolytic activity. CONCLUSION: B*5701+ and B5703+ donors demonstrate broad functional cross-reactivity to both common and rare variants of a dominant p24 epitope, which could be relevant to the association of B*57 alleles with slow progression to AIDS.

Amino Acid Sequence↗

PubMed2002

Gonococcal cervicitis is associated with reduced systemic CD8+ T cell responses in human immunodeficiency virus type 1-infected and exposed, uninfected sex workers.

Neisseria gonorrhoeae cervicitis and human immunodeficiency virus (HIV) type 1 frequently coinfect core transmitter populations, such as female sex workers. Gonococcal cervicitis is associated with increased viral shedding and plasma viremia in HIV-1-infected women and increased HIV-1 susceptibility in uninfected women. We studied the influence of gonococcal cervicitis on CD8(+) interferon (IFN)-gamma responses to HIV-1 and cytomegalovirus (CMV) epitopes in HIV-1-infected and in highly-exposed, persistently seronegative (HEPS) female sex workers. In HIV-1-infected women, gonococcal cervicitis was associated with reduced IFN-gamma responses in bulk CD8(+) lymphocyte populations, and intracellular cytokine staining, combined with class I major histocompatibility complex (MHC)-peptide tetramer studies, demonstrated reduced IFN-gamma production by HIV-1 epitope-specific CD8(+) lymphocytes. In HEPS sex workers, cervicitis was associated with the transient loss of systemic HIV-1-specific CD8(+) responses and with reduced function of CMV-specific CD8(+) lymphocytes. Impaired function of virus-specific CD8(+) lymphocytes may partly explain the deleterious effects of gonococcal cervicitis on HIV-1 immune control and susceptibility.

CD8-Positive T-Lymphocytes↗