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Stepping down resident memory lane
The antigen-specific CD8+ T response to microbial infection includes the differentiation of a subset of CD8+ T cells into tissue-resident memory (TRM) cells that stop circulating and become confined within a nonlymphoid tissue. Kurd et al. used single-cell RNA sequencing of mouse CD8+ T cells at multiple time points during the first 90 days after viral infection to characterize how this differentiation process unfolds in the small intestine and tracks the emergence of heterogeneity among TRM cells. They found evidence for TRM cell precursors in the intestine by 4 days after infection and identified several putative regulators of TRM cell differentiation. The results of this study provide a valuable transcriptomic atlas that will facilitate further investigation into immune functions provided by TRM cells.
Abstract
During an immune response to microbial infection, CD8+ T cells give rise to distinct classes of cellular progeny that coordinately mediate clearance of the pathogen and provide long-lasting protection against reinfection, including a subset of noncirculating tissue-resident memory (TRM) cells that mediate potent protection within nonlymphoid tissues. Here, we used single-cell RNA sequencing to examine the gene expression patterns of individual CD8+ T cells in the spleen and small intestine intraepithelial lymphocyte (siIEL) compartment throughout the course of their differentiation in response to viral infection. These analyses revealed previously unknown transcriptional heterogeneity within the siIEL CD8+ T cell population at several stages of differentiation, representing functionally distinct TRM cell subsets and a subset of TRM cell precursors within the tissue early in infection. Together, these findings may inform strategies to optimize CD8+ T cell responses to protect against microbial infection and cancer.
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