Distinct Diseases Evoke Distinct Weary T cells, Study Finds
Persistent viral infections and tumors drive development of exhausted T (TEX) cells. In these settings, TEX cells establish an important host-pathogen or host-tumor stalemate. However, TEX cells erode over time, leading to loss of pathogen or cancer containment.
Now, researchers at the Perelman School of Medicine at the University of Pennsylvania have found nine distinct types of these “Tex” cells, which could have implications for fighting chronic infections, autoimmunity, and cancer.
“Exhausted T cells are a discrete cell lineage that have become important immunotherapy targets for chronic infection and cancer,” said senior author John Wherry, PhD, a professor ofMicrobiology and director of the Institute for Immunology. “Now, we know that exhausted T cells are a vastly diverse set of immune cells.”
“Exhausted T cells are quite diverse, as are all types of T cells,” Wherry said. “This sheer diversity is the hallmark of the human immune system that has to essentially have a way to respond to every germ an individual might encounter in a lifetime.”
Therefore, the Penn team asked what exactly the diversity at the Tex pool shows about a disorder itself and its own course in an individual.
They developed an assay to
look into the molecules which control gene expression from Tex by comparing these to other kinds of T cells and also inside a Tex population in blood of HIV patients whose viral load is well-controlled. They identified core exhaustion-specific genes and recognized disease-induced molecular fluctuations in Tex populations of HIV with uncontrolled disease and in lung cancer.With this data, the Tex fell into nine different clusters of comparable expression patterns concerning transcription factors and inhibitory receptors.
Due to the clusters’ connections to particular disease type and development, the group’s goal is to utilize the signature of a Tex cluster to estimate a patient’s overall immune health and chances of reacting to a specific treatment.
“We want to be able to select and tailor immune therapies according to a patient’s exhausted T cell pool and its individual characteristics,” Wherry said.
