Heterogeneous Differentiation Patterns of Individual CD8+ T Cells

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Science  14 Mar 2013:
DOI: 10.1126/science.1235487

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Upon infection, antigen-specific CD8+ T lymphocyte responses display a highly reproducible pattern of expansion and contraction that is thought to reflect a uniform behavior of individual cells. We tracked the progeny of individual mouse CD8+ T cells by in vivo lineage tracing and demonstrated that, even for T cells bearing identical T cell receptors, both clonal expansion and differentiation patterns are heterogeneous. As a consequence, individual naïve T lymphocytes contributed differentially to short- and long-term protection, as revealed by participation of their progeny during primary versus recall infections. The discordance in fate of individual naïve T cells argues against asymmetric division as a singular driver of CD8+ T cell heterogeneity and demonstrates that reproducibility of CD8+ T cell responses is achieved through population averaging.

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