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T cell development

Doubling down to make killer T cells

Nature Immunology volume 24, pages 1407–1408 (2023)Cite this article

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Control of the alternative commitment of immature CD4+CD8+ T cells to the CD4+ or CD8+ lineage has long been the subject of intense scrutiny. A combination of CITE-seq and functional assays provides significant new insights into the distinct T cell antigen receptor signaling requirements for these lineage fates.

In the first part of their study1, the authors validate the underlying methodology and show that cell clusters derived from CITE-seq (cellular indexing of transcriptomes and epitopes by sequencing) correspond well to previously identified flow-based thymocyte fractions. Results fit nicely with the kinetic signaling model, showing that the two lineages diverge at the CD4+CD8lo stage based on differential expression of Cd8a mRNA, and that MHC-I- but not MHC-II-specific thymocytes pass through a subsequent double-positive phase (DP3) between the CD4+CD8lo and CD8+ single-positive lineage, characterized by elevated TCR expression. The expression kinetics of the transcription factor–encoding genes Zbtb7b and Runx3 also agree with previous studies, showing low expression of Zbtb7b mRNA in MHC-I-specific CD4+CD8lo cells.

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Fig. 1: Distinct TCR signaling requirements for commitment of immature double-positive CD4+CD8+ cells to the single-positive CD4+ or CD8+ lineage.

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  1. Nuclear Dynamics and Cancer Program, Fox Chase Cancer Center, Philadelphia, PA, USA

    Dietmar Kappes & David L. Wiest

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  1. Dietmar Kappes
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  2. David L. Wiest
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Correspondence to Dietmar Kappes.

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The authors declare no competing interests.

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Kappes, D., Wiest, D.L. Doubling down to make killer T cells. Nat Immunol 24, 1407–1408 (2023). https://doi.org/10.1038/s41590-023-01593-z

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