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WIREs Syst Biol Med
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Single‐cell analysis of CD8 T lymphocyte diversity during adaptive immunity

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Abstract An effective adaptive immune response to microbial infection relies on the generation of heterogeneous T lymphocyte fates and functions. CD8 T lymphocytes play a pivotal role in mediating immediate and long‐term protective immune responses to intracellular pathogen infection. Systems‐based analysis of the immune response to infection has begun to identify cell fate determinants and the molecular mechanisms underpinning CD8 T lymphocyte diversity at single‐cell resolution. Resolving CD8 T lymphocyte heterogeneity during adaptive immunity highlights the advantages of single‐cell technologies and computational approaches to better understand the ontogeny of CD8 T cellular diversity following infection. Future directions of integrating single‐cell multiplex approaches capitalize on the importance of systems biology in the understanding of immune CD8 T cell differentiation and functional diversity. This article is categorized under: Physiology > Mammalian Physiology in Health and Disease Biological Mechanisms > Cell Fates
Hypothetical early divergent model of CD8 T cell differentiation during adaptive immunity. Upon microbial infection, a single naïve CD8 T cell is activated and undergoes cell division for clonal expansion and differentiation into effector and memory T cell subsets. Shown are activated T cells during the course of a microbial infection (including activated naïve T cell, “pre‐effector” and “prememory” cells at early “transitional” stages of differentiation, terminally differentiated effector, long‐lived effector, and memory T cells). Cell‐intrinsic and ‐extrinsic signals (e.g., cytokines, chemokines, cross‐talk with CD4 T cells, APCs, and CD8 T cells) influence the formation of CD8 T cell fate diversity. Abbreviation: APC, antigen‐presenting cell. Image was created with biorender.com
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Integration of deep profiling single‐cell technologies and systems‐based analyses to better understand CD8 T cell fate diversification during adaptive immunity. At the initiation of an adaptive immune response to infection, antigen recognition and presentation by an APC to a naïve CD8 T cell stimulates T cell activation, followed by T cell division, clonal expansion, and effector and memory T cell differentiation. Shown are naïve and activated T cells following primary infection (including hypothetical cells at early “transitional” stages of differentiation, terminal effector and memory cells). Single T cells are subjected to downstream single‐cell molecular profiling at different levels of regulation: transcription, epigenetics, proteomics, biophysical profiling, and spatial organization. Molecular profiling of single cells derived from secondary lymphoid organs (e.g., spleen, lymph nodes), blood, and tissues is depicted. Integration of single‐cell molecular and cellular profiling techniques will facilitate a comprehensive systems analysis of CD8 T cell fate diversification during the immune response to infection. Abbreviations: APC, antigen presenting cell; TEM, effector memory T cell; TCM, central memory T cell; TRM, tissue resident memory T cell; TCR‐seq, T cell receptor sequencing. Image was created with biorender.com
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Biological Mechanisms > Cell Fates
Physiology > Mammalian Physiology in Health and Disease

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