Transcriptional and Epigenetic Regulation of Effector and Memory CD8 T Cell Differentiation

Immune protection and lasting memory are accomplished through the generation of phenotypically and functionally distinct CD8 T cell subsets. Understanding how these effector and memory T cells are formed is the first step in eventually manipulating the immune system for therapeutic benefit. In this review, we will summarize the current understanding of CD8 T cell differentiation upon acute infection, with a focus on the transcriptional and epigenetic regulation of cell fate decision and memory formation. Moreover, we will highlight the importance of high throughput sequencing approaches and single cell technologies in providing insight into genome-wide investigations and the heterogeneity of individual CD8 T cells

Determination of Molecular Structures of HIV Envelope Glycoproteins using Cryo-Electron Tomography and Automated Sub-tomogram Averaging

Since its discovery nearly 30 years ago, more than 60 million people have been infected with the human immunodeficiency virus (HIV) (www.usaid.gov). The virus infects and destroys CD4+ T-cells thereby crippling the immune system, and causing an acquired immunodeficiency syndrome (AIDS) 2. Infection begins when the HIV Envelope glycoprotein "spike" makes contact with the CD4 receptor on the surface of the CD4+ T-cell. This interaction induces a conformational change in the spike, which promotes interaction with a second cell surface co-receptor 5,9. The significance of these protein interactions in the HIV infection pathway makes them of profound importance in fundamental HIV research, and in the pursuit of an HIV vaccine

Induction motors with modulated terminal voltage

Bibliography: pages 292-294.Following the development of high speed solid state switches for the forced commutation of current in AC power circuits it has become feasible to apply forced commutation techniques to the frequency and voltage control of induction motors as variable speed drives. The availability of these methods raises questions regarding their effect on the performance of the motor and the generation of harmonic currents in the electrical supply. After the initial use of numerical simulation in the study of these systems it became apparent that this approach was not suitable for the evaluation of steady state performance factors. This thesis sets out to establish an analysis of the induction motor under these conditions which leads to the algebraic formulation of the performance of the system in the steady state. This approach can be used in any situation where the electrical supply to an induction motor is modulated by switching techniques. The analysis has been applied to chopper modulation of the supply voltage and also to a phase-stepping frequency convertor which incorporates chopper modulation. Experimental results are included to illustrate the validity of the analytical method

Pathogen boosted adoptive cell transfer immunotherapy to treat solid tumors

Because of insufficient migration and antitumor function of transferred T cells, especially inside the immunosuppressive tumor microenvironment (TME), the efficacy of adoptive cell transfer (ACT) is much curtailed in treating solid tumors. To overcome these challenges, we sought to reenergize ACT (ReACT) with a pathogen-based cancer vaccine. To bridge ACT with a pathogen, we genetically engineered tumor-specific CD8 T cells in vitro with a second T-cell receptor (TCR) that recognizes a bacterial antigen. We then transferred these dual-specific T cells in combination with intratumoral bacteria injection to treat solid tumors in mice. The dual-specific CD8 T cells expanded vigorously, migrated to tumor sites, and robustly eradicated primary tumors. The mice cured from ReACT also developed immunological memory against tumor rechallenge. Mechanistically, we have found that this combined approach reverts the immunosuppressive TME and recruits CD8 T cells with an increased number and killing ability to the tumors