Reduced vacuolar ATPase protects mice from Friend virus infection - an unintended but instructive effect in Hif-2afl mice.

During acute viral infections, innate immune cells invade inflamed tissues and face hypoxic areas. Hypoxia-inducible factors (HIFs) adapt cellular responses towards these conditions. We wanted to investigate the effects of a loss of HIF-2α in macrophages during acute Friend murine leukemia retrovirus (FV) infection in C57BL/6 mice using a Cre/loxP system.

Rat cytomegalovirus efficiently replicates in dendritic cells and induces changes in their transcriptional profile.

Dendritic cells (DC) play a crucial role in generating and maintaining antiviral immunity. While DC are implicated in the antiviral defense by inducing T cell responses, they can also become infected by Cytomegalovirus (CMV). CMV is not only highly species-specific but also specialized in evading immune protection, and this specialization is in part due to characteristic genes encoded by a given virus.

Cytotoxic CD4 T cells in chronic viral infections and cancer.

CD4 T cells play an important role in immune responses against pathogens and cancer cells. Although their main task is to provide help to other effector immune cells, a growing number of infections and cancer entities have been described in which CD4 T cells exhibit direct effector functions against infected or transformed cells. The most important cell type in this context are cytotoxic CD4 T cells (CD4 CTL).

Immunotherapy-induced cytotoxic T follicular helper cells reduce numbers of retrovirus-infected reservoir cells in B cell follicles.

Antiretroviral therapy (ART) transformed HIV from a life-threatening disease to a chronic condition. However, eliminating the virus remains an elusive therapy goal. For several decades, Friend virus (FV) infection serves as a murine model to study retrovirus immunity.

Immune suppression of vaccine-induced CD8 T-cell responses by gamma retrovirus envelope is mediated by interleukin-10-producing CD4 T cells.

Retroviral envelope (Env) proteins have long been recognized to exhibit immunosuppressive properties, which affect the CD8 T-cell response to an infection but also to immunization. Interestingly, we previously showed in the Friend murine leukemia virus (F-MuLV) model that the surface Env protein gp70 also plays a role in immunosuppression, in addition to the immunosuppressive function attributed to the transmembrane Env protein. We now demonstrate that immunization with F-MuLV Env leads to a significant increase in interleukin-10 (IL-10)-producing CD4 T cells and that the induction of CD8 T-cell responses in the presence of Env is rescued if the capacity of CD4 T cells to produce IL-10 is abrogated, indicating a mechanistic role of IL-10-producing CD4 T cells in mediating the Env-induced suppression of CD8 T-cell responses in Env co-immunization.

A detailed analysis of F-MuLV- and SFFV-infected cells in Friend virus-infected mice reveals the contribution of both F-MuLV- and SFFV-infected cells to the interleukin-10 host response.

Background: Friend virus (FV) is a complex of the Friend murine leukemia virus (F-MuLV) and the replication-defective, pathogenic spleen focus forming virus (SFFV). In the past, we used a fluorescently labeled F-MuLV to analyze FV target cells. To build on these findings, we have now created a double-labeled FV that contains a Katushka-labeled F-MuLV and an mTagBFP-labeled SFFV, which we have used to study the infection by the two individual viruses in the FV infection of highly susceptible BALB/c mice.

Immunotherapy With Interferon α11, But Not Interferon Beta, Controls Persistent Retroviral Infection.

Type I Interferons (IFNs), including numerous IFNα subtypes and IFNβ, are key molecules during innate and adaptive immune responses against viral infections. These cytokines exert various non-redundant biological activities, although binding to the same receptor. Persistent viral infections are often characterized by increased IFN signatures implicating a potential role of type I IFNs in disease pathogenesis.

Differential regulatory effect of progesterone on the proliferation and apoptosis of uterine leiomyoma tissue explants and primary leiomyoma cell cultures.

Objective: The growth of uterine leiomyomas is regulated by progesterone, although the underlying molecular mechanisms are not fully understood.

Methods: Primary leiomyoma cells were isolated by standard method from 16 samples of uterine leiomyoma tissue. Uterine leiomyoma explants and primary leiomyoma cell cultures were exposed to progesterone in concentrations of 0.

IL-10-producing Tfh cells accumulate with age and link inflammation with age-related immune suppression.

Aging results in profound immune dysfunction, resulting in the decline of vaccine responsiveness previously attributed to irreversible defects in the immune system. In addition to increased interleukin-6 (IL-6), we found aged mice exhibit increased systemic IL-10 that requires forkhead box P3-negative (FoxP3), but not FoxP3, CD4T cells. Most IL-10-producing cells manifested a T follicular helper (Tfh) phenotype and required the Tfh cytokines IL-6 and IL-21 for their accrual, so we refer to them as Tfh10 cells.

Inhibition of IL-2 or NF-B Subunit c-Rel-Dependent Signaling Inhibits Expansion of Regulatory T Cells During Acute Friend Retrovirus Infection.

In retroviral infections, different immunological mechanisms are involved in the development of a chronic infection. In the Friend virus (FV) model, regulatory T cells (Tregs) were found to induce CD8 T cell dysfunction before viral clearance is achieved and thus contribute to viral chronicity. Although studied for decades, the exact suppressive mechanisms of Tregs in the FV model remain elusive and an unavailable therapeutic target.

Diverse Immunomodulatory Effects of Individual IFNα Subtypes on Virus-Specific CD8 T Cell Responses.

Clinical administration of Interferon α (IFNα) resulted in limited therapeutic success against some viral infections. Immune modulation of CD8 T cell responses during IFNα therapy is believed to play a pivotal role in promoting viral clearance. However, these clinical studies primarily focused on IFNα subtype 2.

Immunization with a murine cytomegalovirus based vector encoding retrovirus envelope confers strong protection from Friend retrovirus challenge infection.

Immunization vectors based on cytomegalovirus (CMV) have attracted a lot of interest in recent years because of their high efficacy in the simian immunodeficiency virus (SIV) macaque model, which has been attributed to their ability to induce strong, unusually broad, and unconventionally restricted CD8+ T cell responses. To evaluate the ability of CMV-based vectors to mediate protection by other immune mechanisms, we evaluated a mouse CMV (MCMV)-based vector encoding Friend virus (FV) envelope (Env), which lacks any known CD8+ T cell epitopes, for its protective efficacy in the FV mouse model. When we immunized highly FV-susceptible mice with the Env-encoding MCMV vector (MCMV.

Infection of B Cell Follicle-Resident Cells by Friend Retrovirus Occurs during Acute Infection and Is Maintained during Viral Persistence.

B cell follicles of the spleen and lymph nodes are immune privileged sites and serve as sanctuaries for infected CD4 cells in HIV infection. It is assumed that CD8 T cell responses promote the establishment of the reservoir, as B cell follicles do not permit CD8 T cell entry. Here we analyzed the infected cell population in the Friend retrovirus (FV) infection and investigated whether FV can similarly infect follicular cells.

Chronic retroviral infection of mice promotes tumor development, but CD137 agonist therapy restores effective tumor immune surveillance.

T cell responses are crucial for anti-tumor immunity. In chronic viral infections, anti-tumor T cell responses can be compromised due to various immunological mechanisms, including T cell exhaustion. To study mechanisms of anti-tumor immunity during a chronic viral infection, we made use of the well-established Friend virus (FV) mouse model.

The Cytotoxic Activity of Natural Killer Cells Is Suppressed by IL-10 Regulatory T Cells During Acute Retroviral Infection.

Natural killer (NK) cells play a key role in host defense against cancer and viral infections. It was shown that NK cells are important for the control of acute retroviral infections, but their antiviral activity depends on multiple parameters such as viral inoculation dose, interactions with myeloid cell types and the cytokine milieu. In addition, during an ongoing retroviral infection regulatory T cells (Tregs) can suppress NK cell functions.

Fas Ligand-mediated cytotoxicity of CD4+ T cells during chronic retrovirus infection.

CD4+ helper T cells and cytotoxic CD8+ T cells are key players for adaptive immune responses against acute infections with retroviruses. Similar to textbook knowledge the most important function of CD4+ T cells during an acute retrovirus infection seems to be their helper function for other immune cells. Whereas there was no direct anti-viral activity of CD4+ T cells during acute Friend Virus (FV) infection, they were absolutely required for the control of chronic infection.

CD137 Agonist Therapy Can Reprogram Regulatory T Cells into Cytotoxic CD4+ T Cells with Antitumor Activity.

Recent successes in immune therapeutic strategies aimed to improve control over tumor growth have sparked hope that long-lived control of cancer through stimulation of the immune system can be possible. However, the underlying immunological mechanisms that are induced by immunotherapeutic strategies are not well understood. In this study, we used the highly immunogenic Friend virus-induced FBL-3 tumor as a model to study the mechanisms of immunological tumor control by CD4(+) T cells in the course of CD137 (4-1BB) agonist immunotherapy in the absence of a CD8 T cell response.

Local immunological markers of different rate of growth of uterine myoma.

The aim of our work was to establish the peculiarities of phenotype profile and functional activity of peritoneal immunocompetent cells of women with different rate of myoma growth. Forty three women with uterine myoma (main group) and 16 healthy women (control group) were recruited for study. According to the growth rate and tumor's size the main group was divided into two clinical subgroups: (1) women with stable small size of uterine myoma (23 patients), (2) women with large size rapidly growing myoma (20 patients).

Cytokine network of eutopic and ectopic endometrium in women with adenomyosis.

Problem: Recent studies showed the impairment of local cytokine balance in women with external endometriosis, but similar findings concerning direct production of cytokines by immunocompetent cells of women with adenomyosis are absent. In this context, investigation of the cytokine synthesis by mononuclear cells (MNCs) infiltrating eutopic and ectopic endometrium is of special interest.

Method Of Study: Concentration of interferon-gamma (IFNgamma), interferon-alpha (IFNalpha), tumour necrosis factor-alpha (TNFalpha), interleukin- 1beta (IL-1beta) and epidermal growth factor (EGF) in supernatants (SNs) of 24-hr cultures of MNCs obtained from eutopic and ectopic endometrium of women with adenomyosis was determined by enzyme-linked immunosorbent assay.