Molecular Mechanisms Support Long-term Immunity - News Center

"Scientists in the laboratory of Weiguo Cui, PhD, professor of Pathology in the Division of Experimental Pathology, have identified novel molecular mechanisms that help specialized T-cells maintain long-term immunity in response to chronic infection and cancer, according to recent findings published in Nature Immunology. Previous work from Cui's laboratory and others revealed that exhausted T-cells, or T-cells that have become dysfunctional after chronic antigen stimulation such as chronic infection and cancer, comprise different subgroups of T-cells."

"One of these subgroups are stem-like progenitor CD8+ T-cells, which help sustain the body's immune response through quiescence (when T-cells are dormant but at the ready to be activated by a foreign antigen), multipotency (the ability to differentiate into different cell types) and self-renewal. Better understanding how these T-cells preserve their stem-like qualities under persistent stimulation can help inform new strategies that enhance CD8+ T-cell response and the effectiveness of immunotherapies, according to Cui."

""These cells are really in it for the long haul," said Cui, who is also a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University and the Center for Human Immunobiology. "We wanted to identify what other factors control the formation as well as long-term existence for this type of T-cell in our body." In the current study, Cui and his team performed single-cell RNA sequencing on antigen-specific CD8+ T-cells isolated from mouse models of chronic infection. Using flow cytometry and immunoblotting techniques to study these cells, the scientists observed that the SATB1 protein is upregulated in progenitor and memory CD8+ T-cells."

Specialized CD8+ T-cells include stem-like progenitor cells that sustain immune responses through quiescence, multipotency and self-renewal despite chronic antigen exposure. Distinct exhausted T-cell subgroups include these progenitor and memory populations that preserve long-term immunity during chronic infection and cancer. Using single-cell RNA sequencing, flow cytometry and immunoblotting on antigen-specific CD8+ T-cells from mouse chronic infection models, researchers found that SATB1 protein is upregulated in progenitor and memory CD8+ T-cells. CRISPR-mediated deletion of SATB1 in isolated CD8+ T-cells revealed that SATB1 is essential to maintain CD8+ T-cell stemness under persistent stimulation, with implications for improving immunotherapy effectiveness.

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