Hepatitis C virus-specific cellular immune responses in individuals with no evidence of infection.

The detection of hepatitis C virus (HCV)-specific T cell responses in HCV-uninfected, presumably unexposed, subjects could be due to an underestimation of the frequency of spontaneously resolving infections, as most acute HCV infections are clinically silent. To address this hypothesis, HCV-specific cellular immune responses were characterized, in individuals negative for an HCV PCR assay and humoral response, with (n = 32) or without (n = 33) risk of exposure to HCV. Uninfected volunteers (n = 20) with a chronically HCV-infected partner were included as positive controls for potential exposure to HCV and HCV infection, respectively.

Relationships between HIV disease history and blood HIV-1 DNA load in perinatally infected adolescents and young adults: the ANRS-EP38-IMMIP study.

Background: Our aim was to study the impact of lifelong human immunodeficiency virus (HIV) disease history on the current immune and virological status of perinatally infected patients reaching adulthood. We evaluated blood cell-associated HIV DNA load as an indicator of cell-associated HIV reservoirs and an independent predictor of disease progression.

Methods: The ANRS-EP38-IMMIP Study included 93 patients aged 15-24 years who were infected with HIV during the perinatal period.

Gamma(c) deficiency precludes CD8+ T cell memory despite formation of potent T cell effectors.

Several cytokines (including IL-2, IL-7, IL-15, and IL-21) that signal through receptors sharing the common gamma chain (gamma(c)) are critical for the generation and peripheral homeostasis of naive and memory T cells. Recently, we demonstrated that effector functions fail to develop in CD4(+) T cells that differentiate in the absence of gamma(c). To assess the role of gamma(c) cytokines in cell-fate decisions that condition effector versus memory CD8(+) T cell generation, we compared the response of CD8(+) T cells from gamma(c)(+) or gamma(c)(-) P14 TCR transgenic mice after challenge with lymphocytic choriomeningitis virus.

In untreated HIV-1-infected children, PBMC-associated HIV DNA levels and cell-free HIV RNA levels are correlated to distinct T-lymphocyte populations.

Background: Clinical studies support biologically independent roles of cell-free HIV particles and HIV-infected cells in disease progression. The associations between the level of infected cells and immune markers have been poorly studied, particularly in perinatally infected children.

Objective: We tested the hypothesis that independent roles of cell-free virus and infected cells in HIV pathogenesis should be revealed by different associations between each of them and specific immune markers.

Epitope specificity and relative clonal abundance do not affect CD8 differentiation patterns during lymphocytic choriomeningitis virus infection.

To evaluate the impact of immunodominance on CD8 T-cell properties, we compared the functional properties of dominant and subdominant populations in the response to lymphocytic choriomeningitis virus (LCMV). To improve functional discrimination, in addition to the usual tests of phenotype and function, we used a sensitive technique that allows the screening of all CD8 effector genes simultaneously in single cells. Surprisingly, these methods failed to reveal a major impact of clonal dominance in CD8 properties throughout the response.

Poor recognition of HIV-1 Nef protein by CD8 T cells from HIV-1-infected children: impact of age.

Recognition of various HIV proteins by CD8 T cells from HIV-infected children was determined by two functional assays. First, using an Elispot assay, we show that 80% of patients recognized Gag, 77% recognized Pol, 61% recognized Env, 44% recognized Nef and 29% recognized Vif. Frequencies of Gag-, Pol-, and Env-specific IFN-gamma producing CD8 T cells were higher than frequencies of Nef and Vif-specific CD8 T cells.

The frequency of HIV-specific interferon- gamma -producing CD8 T cells is associated with both age and level of antigenic stimulation in HIV-1-infected children.

Ex vivo interferon (IFN)- gamma -producing CD8 T cells specific for human immunodeficiency virus (HIV) Env, Gag, and Pol antigens were measured in the peripheral blood of 55 children not receiving highly active antiretroviral therapy (HAART) and 70 children receiving HAART. In children not receiving HAART, the frequency of HIV-specific IFN- gamma -producing CD8 T cells was positively correlated with age and was not associated with plasma viral load or CD4 T cell levels. In children receiving HAART, the frequency of HIV-specific IFN- gamma -producing CD8 T cells was directly correlated with plasma viral load, and its association with age remained significant.

In vivo induction of cellular and humoral immune responses by hybrid DNA vectors encoding simian/human immunodeficiency virus/hepatitis B surface antigen virus particles in BALB/c and HLA-A2-transgenic mice.

To improve the immunogenicity of epitopes derived from Gag proteins of simian immunodeficiency virus (SIV) and from the envelope (Env) protein of human immunodeficiency virus type 1 (HIV-1), we have designed hybrid DNA vaccines by inserting sequences encoding antigenic domains of SIV and HIV-1 into the hepatitis B virus envelope gene. This gene encodes the hepatitis B surface antigen (HBsAg) capable of spontaneous assembly into virus-like particles that were used here as carrier. Injections of hybrid vectors encoding B-cell epitopes from the gp41 and the gp120 envelope proteins of HIV-1 induced specific humoral responses in BALB/c mice.

In HIV type 1-infected children cytotoxic T lymphocyte responses are associated with greater reduction of viremia under antiretroviral therapy.

The evolution of the HIV-specific CD8+ T cell response in patients receiving potent combination therapy has been well documented in adult patients. However, no study reported whether baseline HIV-specific CD8+ T cell response is linked to treatment outcome. The aims of this study were to investigate both the impact of baseline memory cytotoxic T lymphocytes (CTL) on treatment outcome and the effect of potent therapy on memory HIV-specific CTL in HIV-1-infected pediatric patients.

The core-specific precursor T cell response is directed to the N-terminal and central parts of the protein and positively correlates to the viral load in chronically HCV-infected patients.

The cellular immune response to hepatitis C virus (HCV) plays a critical role in determining the clearance or persistence of HCV. Moreover, in chronic HCV infection, these responses that are insufficient to eradicate virus completely may cause liver injury. In this study, the memory T cells responses specific to the core protein were measured by interferon-gamma Elispot assay after in vitro stimulation of peripheral blood mononuclear lymphocytes from chronically infected subjects.

Loss of reactivity of vaccine-induced CD4 T cells in immunized monkeys after SIV/HIV challenge.

Background: Immunization protocols involving priming with DNA and boosting with recombinant live virus vectors such as recombinant modified Vaccinia Ankara (rMVA) are considered as vaccine candidates against HIV. Such protocols improve the outcome of simian/human immunodeficiency virus (SHIV) pathogenic challenge in Rhesus monkeys.

Objectives: To investigate the fate of vaccine-induced T cells after a mucosal SHIV challenge.

A vaccinia-based elispot assay for detection of CD8+ T cells from HIV-1 infected children.

HIV-specific CD8+ T lymphocytes participate in the control of viral replication in infected patients. These responses are of low intensity in young infants and are decreased by antiretroviral therapy. In the present study, we report on a recombinant Vaccinia virus (rVV)-based Elispot assay for the detection of HIV-specific CD8+ T cells immediately after isolation of peripheral blood mononuclear cells (PBMC).

Not all tetramer binding CD8+ T cells can produce cytokines and chemokines involved in the effector functions of virus-specific CD8+ T lymphocytes in HIV-1 infected children.

In the pediatric human immunodeficiency virus type-1 (HIV-1) infection, the presence of cytotoxic T lymphocytes (CTL) is associated with a slow progression to AIDS. The secretion of cytokines by CTLs may be critical in the control of viral infection. We used the combination of cell surface and intracellular staining to study the functionality of tetramer binding CD8+ T cells recognizing two HIV-1 immunodominant epitopes, in peripheral blood mononuclear cells from HIV-1-infected children.

Efficient priming of simian/human immunodeficiency virus (SHIV)-specific T-cell responses with DNA encoding hybrid SHIV/hepatitis B surface antigen particles.

Recent efforts to design an human immunodeficiency virus type 1 (HIV-1) vaccine candidate have focused on means of eliciting anti-viral T-cell responses. We tried to improve the immunogenicity of DNA vaccines by designing hybrid DNA constructs encoding hepatitis B surface antigen (HBsAg) fused to antigenic domains of simian/human immunodeficiency virus (SHIV 89.6P).

Functional characterization of human Tc0, Tc1 and Tc2 CD8+ T cell clones: control of X4 and R5 HIV strain replication.

CD8(+) T lymphocytes have the potential ability to inhibit human immunodeficiency virus (HIV) replication, by secreting soluble(s) factor(s) known as CD8(+) T lymphocyte antiviral factor (CAF). A panel of CD8(+) and CD4(+) T cell clones from HIV1-infected and uninfected donors were generated to better define the phenotype of CAF-producing cells. We first verified that the different CD4(+) T cell subsets (Th0, Th1, and Th2) were productively infected by X4 and R5 virus strains.

Kinetics of lymphocyte proliferation during primary immune response in macaques infected with pathogenic simian immunodeficiency virus SIVmac251: preliminary report of the effect of early antiviral therapy.

The aim of this study was to evaluate the kinetics of lymphocyte proliferation during primary infection of macaques with pathogenic simian immunodeficiency virus (SIV) and to study the impact of short-term postexposure highly active antiretroviral therapy (HAART) prophylaxis. Twelve macaques were infected by intravenous route with SIVmac251 and given treatment for 28 days starting 4 h postexposure. Group 1 received a placebo, and groups 2 and 3 received combinations of zidovudine (AZT), lamivudine (3TC), and indinavir.

Extensive apoptosis in lymphoid organs during primary SIV infection predicts rapid progression towards AIDS.

Objective: The acute phase of HIV and SIV infections leads to a host/virus equilibrium, and accumulating evidence suggests that this early phase dictates further progression towards AIDS. To gain insight into the early events that determine rapid disease progression, we performed a longitudinal study in the SIV rhesus macaque model, allowing an in-depth analysis of the primary stage of infection.

Methods: We assessed viral replication (quantification of replicating and infected cells in lymph nodes, plasma viral load), immune response (cytotoxic T lymphocyte, antibody, proliferative responses), apoptosis and cycling cells (Ki-67 labelling) on lymph nodes and blood in nine rhesus macaques infected with the pathogenic SIVmac251 isolate.

Correlation between breadth of memory HIV-specific cytotoxic T cells, viral load and disease progression in HIV infection.

Background: Memory cytotoxic T lymphocytes (CTL) should play a key role in controlling HIV infection. The correlations between the breadth and specificities of memory CTL and virus production and disease progression are still unknown, but are of major importance for vaccine strategies.

Methods And Design: One-hundred and forty-eight chronically-infected patients, enrolled before the advent of highly active antiretroviral therapy, were followed-up prospectively over 5 years.

Inverse correlation between memory Gag-specific cytotoxic T lymphocytes and viral replication in human immunodeficiency virus-infected children.

A previous study showed that, during the first year of life, the presence of cytotoxic T lymphocytes (CTLs) in human immunodeficiency virus (HIV)-infected children is associated with a lack of rapid progression to acquired immunodeficiency syndrome. The goal of the study was to address the role of CTLs in children who survived after age 5 years. Memory HIV-specific CTLs directed against Env, Gag, Nef, and Pol proteins were measured in a group of 47 highly active antiretroviral therapy-naive HIV-infected children.

Frequencies of ex vivo-activated human immunodeficiency virus type 1-specific gamma-interferon-producing CD8+ T cells in infected children correlate positively with plasma viral load.

HIV-specific CD8+ T cells are critical in controlling human immunodeficiency virus (HIV) replication. We present the evaluation of a gamma-interferon (IFN-gamma)-based enzyme linked immunospot (ELISPOT) assay for the quantification of HIV-specific CD8+ T cells from HIV-infected children. We studied 20 HLA-A*0201-positive HIV-infected children.

Lack of an immune response against the tetracycline-dependent transactivator correlates with long-term doxycycline-regulated transgene expression in nonhuman primates after intramuscular injection of recombinant adeno-associated virus.

We previously documented persistent regulation of erythropoietin (Epo) secretion in mice after a single intramuscular (i.m.) injection of a recombinant adeno-associated virus (rAAV) vector harboring both the tetracycline-dependent transactivator (rtTA) and the Epo cDNA (D.