ovalbumin and Retroviridae-Infections

Adenovirus (AdV)-based vectors are popular experimental vaccine vectors, but despite their ability to induce strong immune responses, their application is impeded by widespread preexisting immunity against many AdV types that can impair or even abrogate the induction of transgene-specific immune responses. Therefore, the development of vectors based on AdV types with a low seroprevalence is important for effective AdV-based immunization in humans. We investigated the immunization efficacy of vectors based on AdV type 48 (Ad48) and Ad50 in the ovalbumin (ova) model as well as the Friend retrovirus (FV) model, which allows testing of the protective effect of vaccine-induced immunity. Using ova-encoding vectors, we found a significantly lower induction of ova-specific CD8

Topics: Adenoviridae; Adenoviridae Infections; Adenovirus Vaccines; Animals; Antibodies, Viral; Antigens, Viral; CD8-Positive T-Lymphocytes; Female; Genetic Vectors; Humans; Immunity, Cellular; Immunization; Mice; Mice, Inbred BALB C; Ovalbumin; Retroviridae; Retroviridae Infections

Commensal microbes are often required to control viral infection by facilitating host immune defenses. However, we found that this does not hold true for retroviral infection. We report that retrovirus-resistant mice control the pathogen with virus-neutralizing antibodies independently of commensal microbiota. This is in contrast to orthomyxoviruses and arenaviruses, where resistance is ablated in animals depleted of microbiota. Clearly, when it comes to antiviral immunity, the role of the microbiota cannot be generalized.

Topics: Animals; Antibodies, Neutralizing; Blotting, Western; Enzyme-Linked Immunosorbent Assay; Freund's Adjuvant; Germ-Free Life; Immunity, Humoral; Mice; Mice, Inbred Strains; Microbiota; Ovalbumin; Retroviridae Infections; Species Specificity; Specific Pathogen-Free Organisms

When used as therapy for hematopoietic malignancies, allogeneic BM transplantation (BMT) relies on the graft-versus-leukemia (GVL) effect to eradicate residual tumor cells through immunologic mechanisms. However, graft-versus-host disease (GVHD), which is initiated by alloreactive donor T cells that recognize mismatched major and/or minor histocompatibility antigens and cause severe damage to hematopoietic and epithelial tissues, is a potentially lethal complication of allogeneic BMT. To enhance the therapeutic potential of BMT, we sought to find therapeutic targets that could inhibit GVHD while preserving GVL and immune responses to infectious agents. We show here that T cell responses triggered in mice by either Listeria monocytogenes or administration of antigen and adjuvant were relatively well preserved in the absence of PKC isoform theta (PKCtheta), a key regulator of TCR signaling. In contrast, PKCtheta was required for alloreactivity and GVHD induction. Furthermore, absence of PKCtheta raised the threshold for T cell activation, which selectively affected alloresponses. Most importantly, PKCtheta-deficient T cells retained the ability to respond to virus infection and to induce GVL effect after BMT. These findings suggest PKCtheta is a potentially unique therapeutic target required for GVHD induction but not for GVL or protective responses to infectious agents.

Topics: Animals; Bone Marrow Transplantation; Female; Graft vs Host Disease; Graft vs Leukemia Effect; In Vitro Techniques; Isoantigens; Isoenzymes; Leukemia, Experimental; Listeria monocytogenes; Lymphocyte Activation; Male; Mice; Mice, Inbred BALB C; Mice, Knockout; Mice, Transgenic; Ovalbumin; Peptide Fragments; Protein Kinase C; Protein Kinase C-theta; Retroviridae Infections; Signal Transduction; T-Lymphocytes

We previously identified a superantigen from the exogenous mouse mammary tumor virus carried by FM mice [MMTV (FM)], which can preferentially activate V beta 8.2+ CD4+ T cells by subcutaneous injection. In the present study we investigated the effect of neonatal infection with the virus on the T cell receptor (TCR) beta-chain variable region (V beta) repertoire, T cell immune response, and development of experimental allergic encephalomyelitis (EAE). The infection, surprisingly, resulted in deletion of a large portion of CD4+ T cells including V beta 2+, 6+, 8.1+, 8.3+, and 14+ CD4+ T cells in addition to V beta 8.2+ CD4+ T cells. Nevertheless, the infection marginally affected T cell immune response to various antigens such as ovalbumin (OVA) and alloantigen except the abrogated response to anti-V beta 8.2 antibody-mediated receptor cross-linking. Moreover, the infection exerted a protective effect on the development of EAE in (PL/J x SJL)F1 mice. Thus, MMTV (FM) superantigen has the ability to delete a large portion of CD4+ T cells with broad TCR V beta specificity, including V beta 8.2+ CD4+ T cells, and may have potential as a therapeutic agent against autoimmune diseases.

Topics: Animals; Antigens, Viral; CD3 Complex; CD4-Positive T-Lymphocytes; Encephalomyelitis, Autoimmune, Experimental; Isoantigens; Mammary Tumor Virus, Mouse; Mice; Mice, Inbred BALB C; Ovalbumin; Receptors, Antigen, T-Cell, alpha-beta; Retroviridae Infections; Superantigens; Tumor Virus Infections; Vaccination