Antiviral autophagy restrictsRift Valley fever virus infection and is conserved from flies to mammals.

Autophagy has been implicated as a component of host defense, but the significance of antimicrobial autophagy in vivo and the mechanism by which it is regulated during infection are poorly defined. Here we found that antiviral autophagy was conserved in flies and mammals during infection with Rift Valley fever virus (RVFV), a mosquito-borne virus that causes disease in humans and livestock. In Drosophila, Toll-7 limited RVFV replication and mortality through activation of autophagy.

Expression of xenogeneic MHC class II molecules in HLA-DR(+) and -DR(-) cells: influence of retrovirus vector design and cellular context.

We recently established that molecular chimeras of major histocompatibility complex (MHC) class II molecules, created via retroviral transfer of allogeneic class II cDNAs into bone marrow cells (BMCs), alleviated complications associated with mixed BMC chimeras while leading to T cell tolerance to renal grafts sharing the transferred class II. Initially demonstrated for allogeneic transplants in miniature swine, this concept was extended to T-dependent antibody (Ab) responses to xenogeneic antigens (Ags) in the pig --> baboon combination. Successful down-regulation of T cell responses appeared, however, to be contingent on a tight lineage-specific expression of transferred class II molecules.

Efficacy of a therapeutic cocaine vaccine in rodent models.

Cocaine abuse is a major medical and public health concern in the United States, with approximately 2.1 million people dependent on cocaine. Pharmacological approaches to the treatment of cocaine addiction have thus far been disappointing, and new therapies are urgently needed.

Influence of environmental factors on the infectivity of Echinococcus multilocularis eggs.

The sensitivity of eggs of Echinococcus multilocularis to environmental and controlled laboratory conditions was tested. Egg material was exposed and the infectivity was subsequently monitored by in vitro activation and by oral infection of the natural host, Microtus arvalis. To study the impact of environmental conditions in an endemic area of south-western Germany, eggs were sealed into bags of nylon mesh and exposed to the natural climate during various seasons.

A universal T cell epitope-containing peptide from hepatitis B surface antigen can enhance antibody specific for HIV gp120.

Peptide-based vaccines that directly target T cell or B cell epitopes may have significant advantages over conventional vaccines. Further, synthetic chimeric peptides that combine strong T cell epitopes with poorly immunogenic, but immunodominant, B cell epitopes or strain-conserved B cell epitopes may be useful in eliciting antibody to such important regions. Here we characterize a human T cell epitope analyzed in 54 individuals immunized with a hepatitis B virus surface Ag vaccine.

The potential use of T cell epitopes to alter the immune response.

Recent advances in the understanding of T cell specificity and activation have lead to the design of T cell specific immunomodulators. T cell epitope containing peptides have been proposed as agents which may either enhance or dampen the immune response. In this review, we examine two systems which can benefit from the application of this novel technology.

Structure of the T-cell antigen receptor: evidence for two CD3 epsilon subunits in the T-cell receptor-CD3 complex.

The T-cell antigen receptor (TCR) consists of heterodimeric glycoproteins (TCR alpha beta or gamma delta) that demonstrate homology with immunoglobulins. Noncovalently associated with the alpha beta (or gamma delta) heterodimer are at least five nonvariant proteins (CD3-gamma, -delta, -epsilon, -zeta, and -eta), which together comprise the TCR-CD3 complex. The stoichiometry of the antigen receptor has been assumed to be either alpha beta gamma delta epsilon zeta zeta or alpha beta gamma delta epsilon zeta eta.

Prostaglandin E2-dependent induction of B cell unresponsiveness. Role of surface Ig and Fc receptors.

Previously, we demonstrated that two signals were required for accessory cells to induce B cell unresponsiveness: tolerogenic Ig and PG. The purpose of this study was to investigate whether PGE2, in an accessory cellfree system, promoted fluorescein-specific B cell unresponsiveness in conjunction with ligands which bound to surface Ig (sIg) and/or FcR. Several conditions were found whereby PGE2 was obligatory for unresponsiveness.

E-series prostaglandins are potent growth inhibitors for some B lymphomas.

The ability of prostaglandins (PG) to inhibit the growth of B cell lymphomas was investigated. Macrophage-secreted PGE2 was previously shown to promote unresponsiveness to antigen in normal B lymphocytes. This observation suggested that B lymphomas might also be regulated by prostanoids.

Two signals are required for accessory cells to induce B cell unresponsiveness. Tolerogenic Ig and prostaglandin.

We previously demonstrated that a lymphoid dendritic cell-like tumor line (P388AD.2) presented a normally tolerogenic signal, fluoresceinated sheep gamma-globulin (FL-SGG), as an immunogenic one. In contrast, macrophages derived from the peritoneal cavity potentiated the ability of FL-SGG to induce B cell unresponsiveness.

Differential presentation of tolerogenic immunoglobulin in vivo by macrophages and by a lymphoid dendritic cell-like tumor line.

Previous work indicated that macrophages and a lymphoid dendritic cell-like tumor line, P388AD.2, possessed a differential ability to present a haptenated immunoglobulin (tolerogen) in vitro. Macrophages presented fluorescein-conjugated sheep gamma globulin (FL-SGG) and elicited B-cell unresponsiveness.