Biomedical subjects

T H Bian

Publications and source records attributed to T H Bian.

7 recordsLinked to original sources

PubMed2000

Immunobiology of hepatitis C virus (HCV) infection: the role of CD4 T cells in HCV infection.

Hepatitis C virus (HCV) is yet another example of a pathogen that persists in the presence of a readily apparent immune response. As evidence for both humoral and cellular immune responsiveness is quite strong, our studies have begun to examine whether qualitative defects in CD4 T-cell responses to viral antigens may help to explain why HCV is not eliminated in the vast majority of infections. Direct evidence that CD4 T cells play a role in HCV persistence is lacking, but several observations are consistent with this possibility. Importantly, it does not exclude the role of antibody or killer T cells in the immunopathogenesis of HCV infection. In addition, we discuss the consequences of viral mutation and how naturally occurring variants in immunodominant viral epitopes can effectively suppress helper T-cell responses to wild type virus.

Antigen Presentation↗

PubMed1999

Functionally distinct T-cell epitopes within the hepatitis C virus non-structural 3 protein.

Clearance of Hepatitis C Virus (HCV) infection is an uncommon phenomenon. To understand the mechanism of viral persistence despite active cellular and humoral responses, we examined the in vitro cytokine response of PBMC from an HCV sero-positive, asymptomatic individual to recombinant intact antigen and sixty-nine overlapping peptides of the HCV non-structural (NS) 3 protein. Whereas, intact antigen induced strong proliferation and significant levels of gammaIFN and IL-10, little or no IL-2 was produced. Only 7% of peptides induced IL-2, which also coincided with their ability to stimulate proliferation. In contrast, 38% of the peptides induced gammaIFN while 35% induced IL-10. All IL-2 stimulating peptides also induced significant levels of gammaIFN and among these, a peptide corresponding to residues 358-375 was the strongest. In addition, 16% of the peptides induced both gammaIFN and IL-10. Exogenous recombinant IL-10 inhibited proliferation and IL-2 induction in response to peptide 358-375. Furthermore, neutralization of IL-10 with an anti-IL-10 antibody resulted in enhanced IL-2 production in response to recombinant NS3 protein. We suggest that IL-10 inducing epitopes within HCV NS3 may thus down-regulate IL-2 dependent T-cell responses.

Cell Division↗

PubMed1999

In vitro human Th-cell responses to a recombinant hepatitis C virus antigen: failure in IL-2 production despite proliferation.

Hepatitis C Virus (HCV) causes chronic infection in 80-90% of those exposed and persists despite evidence of immune recognition. To understand the immunological basis of this phenomenon, we have synthesized a non structural (NS) protein that is critical to HCV infection and replication, NS3, and used it to study in vitro helper T-cell responses from infected individuals. Strong proliferative responses were generated by peripheral T-cells isolated from a subset of chronically infected patients, but not by normal, non-infected controls. Interestingly, though gamma-interferon (gammaIfn) and IL-10 were both secreted in response to stimulation by NS3 antigen, IL-2 was not. In contrast, IL-2 was secreted in response to influenza virus vaccine antigen. Lack of IL-2 induction was confirmed by a failure to amplify IL-2 mRNA upon NS3 antigen stimulation, whereas IL-4, IL-15, and gammaIfn mRNA were seen as early as 24 h. The predominance of IL-4 and IL-10 and the lack of IL-2 suggests that in vitro responses to at least some HCV antigens are biased towards a Th2 phenotype, which may be conducive to viral persistence.

Hepatitis C↗

PubMed1999

Identification of antigenic escape variants in an immunodominant epitope of hepatitis C virus.

Numerous investigators have postulated that one mechanism by which hepatitis C virus (HCV) may evade the immune system is through the formation of escape mutants. This hypothesis is based largely on the observed mutability of the viral genome resulting in evolution of diverse quasispecies over the course of infection. That such diversification is a product of viral RNA polymerase infidelity, immune-driven selection or a combination of the two processes has not been addressed. We have examined sequence variability in a specific segment of HCV RNA encoding a known immunodominant region of the viral helicase, amino acids 358-375 of the non-structural 3 protein. Using sequence-specific oligonucleotide probe hybridization and automated DNA sequencing, we report a high frequency of mutations, essentially all of which result in amino acid replacements. To assess the biological impact of such mutations, corresponding chemically synthesized peptides were compared to wild-type peptide in T cell proliferation assays. We observed that a sizeable fraction of such peptides stimulated attenuated or negligible levels of proliferation by peripheral T cells from a chronically infected patient. This observation is consistent with expectations for immune-mediated selection of escape variants at the epitope level. We postulate that such a mechanism may be important in the immunopathogenesis of HCV infections.

Base Sequence↗

PubMed1995

Immunomodulating effects of morphine microinjected into periaqueductal gray.

AIM: To study the effects of morphine on immune system through rat brain periaqueductal gray (PAG). METHODS: Three hours after microinjection of morphine through the implanted steel tubes to PAG, splenic cytokines interleukin 2 (IL-2), interleukin 6 (IL-6), tumor necrosis factor (TNF), and natural killer cells (NK) activity were measured. RESULTS: Microinjection of morphine (0.5 microL, 3672 ng) into PAG region had no influence on IL-6 and TNF-alpha (production of splenic macrophages, suppressed the natural killer cell (NK) activity and enhanced T-lymphocyte functions, including concanavalin A (Con A)-induced T-cell proliferation, IL-2 and TNF-beta production. Both the suppressive and stimulating actions were blocked by PAG preinjection of the mu opioid receptor antagonist naloxone (0.5 microL, 1 microgram), which alone showed the contrary effect to morphine. CONCLUSION: Morphine affected immunofunctions through opioid receptors in PAG, and the influences on various immunocompetent cells were different.

Animals↗

PubMed1995

Effects of morphine and naloxone on proliferation of lymphocytes in vitro.

AIM: To study the effects of morphine on different lymphocytes and the influence of naloxone. METHODS: The proliferation rates of unmature, resting, and activated T-lymphocytes and B-lymphocytes were determined under various concentrations of morphine with or without naloxone in vitro. RESULTS: Morphine 1 x 10(-10)-1 x 10(-6) mol L-1 enhanced concanavalin A (Con A)-induced splenic T-cell proliferation, and 1 mumol L-1 enhanced lipopolysaccharide (LPS)-induced splenic B-cell proliferation. Naloxone, which per se enhanced the T-cell proliferation, blocked the enhancing effects of morphine. Morphine (1 x 10(-10)-1 x 10(-5) mol L-1) had no influence on the proliferation of resting splenocytes and Con A-induced thymus cells. Morphine 1 mmol L-1 inhibited the proliferation of resting, LPS-induced splenocytes, and Con A-induced splenic and thymus cells. These inhibiting effects were not blocked by naloxone (50 mumol L-1). CONCLUSION: Stimulating effect of morphine on activated T- and B-cells were mediated by opioid receptors and different opioid receptors existed during the differentiation and activation of lymphocytes. The inhibitory effects of morphine (1 mmol L-1) were not mediated by opioid receptors.

Animals↗

PubMed1995

Effect of morphine on interleukin-1 and tumor necrosis factor alpha production from mouse peritoneal macrophages in vitro.

AIM: To study the influence of morphine on lymphokine production from mouse peritoneal macrophages (PM phi). METHODS: The productions of interleukin-1 (IL-1) and tumor necrosis factor (TNF-alpha) from PM phi under various concentrations of morphine with or without naloxone were measured by testing thymocyte proliferation and L929 cell lysis in vitro. RESULTS: Both morphine (1 x 10(-8) - 1 x 10(-3) mol L-1) and naloxone (50 mumol L-1) inhibited IL-1 production from mouse PM phi primed by sodium thioglycolate. Naloxone did not block the inhibitory effect of morphine. TNF-alpha production from PM phi was inhibited by only high concentration (1 mmol L-1) of morphine which was not blocked by naloxone. CONCLUSION: Morphine had a direct inhibitory effect on PM phi, which was not mediated by opioid receptor of PM phi.

Animals↗