Cross-talk between programmed death-1 and suppressor of cytokine signaling-1 in inhibition of IL-12 production by monocytes/macrophages in hepatitis C virus infection.

Hepatitis C virus (HCV) dysregulates innate immune responses and induces persistent viral infection. We previously demonstrated that HCV core protein impairs IL-12 expression by monocytes/macrophages (M/M(Φ)s) through interaction with a complement receptor gC1qR. Because HCV core-mediated lymphocyte dysregulation occurs through the negative immunomodulators programmed death-1 (PD-1) and suppressor of cytokine signaling-1 (SOCS-1), the aim of this study was to examine their role in HCV core-mediated IL-12 suppression in M/M(Φ)s.

PD-1 modulates regulatory T cells and suppresses T-cell responses in HCV-associated lymphoma.

T regulatory (T(R)) cells suppress T-cell responses that are critical in the development of chronic viral infection and associated malignancies. Programmed death-1 (PD-1) also has a pivotal role in regulation of T-cell functions during chronic viral infection. To examine the role of PD-1 pathway in regulating T(R)-cell functions that inhibit T-cell responses during virus-associated malignancy, T(R) cells were investigated in the setting of hepatitis C virus-associated lymphoma (HCV-L), non-HCV-associated lymphoma (non-HCV-L), HCV infection alone and healthy subjects (HS).

Viral vaccines and CTL response.

Immune induction by successful vaccine formulations seems to involve stimulation of both humoral and cellular arms of immunity. Nevertheless, CD8+ CTLs are of critical relevance in the context of intracellular infection and tumor for many reasons. The task of exerting antipathogen activity by CD8+ T cells, which principally function to control and eradicate intracellular pathogens, is enabled by constitutive expression of MHC class-I molecules on all tissue types.

Heterologous CD8 T cell immune response to HSV induced by toll like receptor ligands.

A memory response is established following primary antigen exposure that stays more or less constant. It appears to adopt a set-point in magnitude but upon re-exposure the response is quicker and better and there is an upward shift in memory frequency that varies with individuals based on the exposure pattern to other microbes or its components. Our investigations were designed to test such differences of non-specific stimulation by PAMPs in lowering the threshold of activation.

T regulatory cells: an overview and intervention techniques to modulate allergy outcome.

Dysregulated immune response results in inflammatory symptoms in the respiratory mucosa leading to asthma and allergy in susceptible individuals. The T helper type 2 (Th2) subsets are primarily involved in this disease process. Nevertheless, there is growing evidence in support of T cells with regulatory potential that operates in non-allergic individuals.

IL-21 and IL-15 cytokine DNA augments HSV specific effector and memory CD8+ T cell response.

The recurrence of lesions and transmission of Herpes simplex virus is dependent on the number and function of viral specific CD8(+) T cells, especially the memory T cells. The generation, turnover and set point of this cell population is maintained by different factors like exposure to antigen, cytokines and co-stimulatory molecules. However, the contribution of these factors in the generation and maintenance of the memory CD8(+) T cell population is still controversial, since it is not clear if homeostatic proliferation driven by cytokines can overcome T cell receptor (TCR) signaling.

Natural killer cells as novel helpers in anti-herpes simplex virus immune response.

Innate defenses help to eliminate infection, but some of them also play a major role in shaping the magnitude and efficacy of the adaptive immune response. With regard to influencing subsequent adaptive immunity, NK cells aided by dendritic cells may be the most relevant components of the innate reaction to herpes simplex virus (HSV) infection. We confirm that mice lacking or depleted of NK cells are susceptible to HSV-induced lesions.

CD4+CD25+ regulatory T cells control the severity of viral immunoinflammatory lesions.

CD4(+)CD25(+) regulatory T cells (T(reg)) can inhibit a variety of autoimmune and inflammatory diseases, but their involvement in regulating virus-induced immunopathology is not known. We have evaluated the role of T(reg) in viral immunopathological lesion stromal keratitis. This frequent cause of human blindness results from a T cell-mediated immunoinflammatory response to HSV in the corneal stroma.

CD4+CD25+ T cells regulate virus-specific primary and memory CD8+ T cell responses.

Naturally occurring CD4+CD25+ regulatory T cells appear important to prevent activation of autoreactive T cells. This article demonstrates that the magnitude of a CD8+ T cell-mediated immune response to an acute viral infection is also subject to control by CD4+CD25+ T regulatory cells (Treg). Accordingly, if natural Treg were depleted with specific anti-CD25 antibody before infection with HSV, the resultant CD8+ T cell response to the immunodominant peptide SSIEFARL was significantly enhanced.

Induction of CD8 T-cell-specific systemic and mucosal immunity against herpes simplex virus with CpG-peptide complexes.

Oligodeoxynucleotides (ODN) containing unmethylated CpG motifs exert powerful adjuvant activity in vivo and in vitro. Administered with antigen they induce a population of antigen-specific CD8+ T cells. In this study we immunized C57BL/6 mice with bioactive CpG ODN combined with an immunodominant epitope derived from herpes simplex virus (HSV) glycoprotein B (amino acids 498 to 505; SSIEFARL) and analyzed the magnitude and durability of the peptide-specific response.