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Recently, California researchers have discovered how CD4 cytotoxic T cells develop, which may open the door to improved HIV and hepatitis C vaccine design. The results of the study were published online in the "Science Immunology" on January 19, 2018.

Science Supplement: New Discovery Provides New Ideas for Improving HIV and Hepatitis C Vaccine

New discovery

For years, scientists around the world have been trying to develop effective HIV and hepatitis C vaccines, but the results have not been satisfactory. Currently, the only way to control these chronic viruses is to use drugs.

In this latest study, researchers at the La Jolla Institute of Allergy and Immunology (LJI) use single-cell transcriptome analysis to identify precursors of deadly T cell subsets that have so far been unknown. There are mainly people with chronic viral infections. They analyzed the transcriptional genomes in more than 9,000 individual cells in detail and revealed unprecedented levels of heterogeneity.

Dr. K. William J. Bowes Jr, the research leader and LJI Distinguished Professor, said: "The evolving genomic tools and single-cell analysis technologies are revolutionizing our understanding of the health and disease of the human immune system. But this is just a genomic journey. At the beginning, by applying these tools to related diseases and cell types, we are changing our understanding of human immune cell biology.

Science Supplement: New Discovery Provides New Ideas for Improving HIV and Hepatitis C Vaccine

It is understood that based on cell surface markers, namely CD4 and CD8, T cells are generally divided into two broad categories: CD4-positive helper T cells (helping to activate other immune cells) and CD8-positive cytotoxic T cells (killing cancer cells or infections). Cells and viruses).

However, in some cases, a portion of helper T cells become cytotoxic T cells (CD4-CTL). CD4 CTL was originally found in humans with chronic viral infections such as human cytomegalovirus (CMV), HIV, dengue virus and hepatitis C virus.

New tool

Dr. Veena Patil, a postdoctoral researcher and first author, said, "We observed an increase in the ratio of cytotoxic CD4 T cells to CD4 helper T cells, suggesting that they are important components of a protective immune response to viral infection, and their induction. It should be an important indicator of successful prevention of certain viral diseases. But we know very little about their molecular structure and the mechanisms that drive their differentiation and maintenance."

To learn more, Patil uses single-cell RNA sequencing to analyze thousands of CD4-CTLs isolated from donor peripheral blood, defining different cell types and subtypes by revealing differences in transcripts produced by individual cells. These analyses reveal significant heterogeneity between individual cells and individuals. “This may be due to the diversity of infections and viral exposure times and the impact of genetic diversity in our subjects,” she said.

Vijayanand and his team discovered previously unknown precursors for this group of T cells, explaining how CD4 killer T cells are formed and can help modulate vaccine designs for viruses such as HIV, hep C and cytomegalovirus.

New ideas

The development of HIV and hepatitis C vaccines has been a challenge because both viruses are rapidly mutating to escape the immune system. Scientists at the AIDS Vaccine Program and the Scripps Research Institute are focusing on viral changes and antibody characteristics, which could be a blueprint for HIV vaccine design.

At the same time, the University of Maryland raised $6 million from the National Institutes of Health (NIH) to develop a hepatitis C vaccine using "structure-based design." The idea is to create vaccine immunogens at the atomic level in order to "stabilize" the antigen and avoid dispersing the elements that rapidly develop the virus.

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