A new type of white blood cell has been identified that activates a killing immune response to an external source—providing a new potential target for vaccines for conditions such as cancer or hepatitis B. Publishing in the journal Immunity, a team of researchers from Newcastle University in collaboration with A*STAR’s Singapore Immunology Network describe a new human tissue dendritic cell (DC) with cross-presenting function.

Most cells are only able to present antigens from within themselves, and so will only elicit an immune response if they are infected themselves. Only a specialized subset of dendritic cells is able to generate a response to an external source of antigen, for example bacteria, vaccines, and tumors.

The identity of human tissue DCs that are capable of presenting external antigen to activate the cell-killing response by T cells—a process termed cross-presentation—has remained a mystery. Their discovery, as revealed by this research, will help scientists to design better targeted vaccine strategies to treat cancer and infections.

“These are the cells we need to be targeting for anticancer vaccines,” says Muzlifah Haniffa, M.D., Ph.D., a Wellcome Trust Intermediate Fellow and senior clinical lecturer at Newcastle University. “Our discovery offers an accessible, easily targetable system that makes the most of the natural ability of the cell.”

The researchers also showed for the first time that dendritic cell subsets are conserved between species and have in effect created a map, facilitating the translation of mouse studies to the human immune system.

The researchers isolated the dendritic cells from human blood and skin and from mouse blood, lung, and liver. Using gene expression analysis, they identified gene signatures for each human dendritic cell subset. Mouse orthologues of these genes were identified, and a computational analysis was performed to match subsets across species.This provides scientists for the first time with an accurate model to compare DCs between species.

“These gene signatures are available in a public repository accessible for all researchers to benefit from the data,” says Dr. Haniffa. “It will allow detailed knowledge of individual human dendritic cell subsets to enable specific targeting of these cells for therapeutic strategy.”

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