Asymmetric cell division safeguards memory CD8 T cell development
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Date
2023-05-30
Publication Type
Journal Article
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yes
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Abstract
The strength of T cell receptor (TCR) stimulation and asymmetric distribution of fate determinants are both implied to affect T cell differentiation. Here, we uncover asymmetric cell division (ACD) as a safeguard mechanism for memory CD8 T cell generation specifically upon strong TCR stimulation. Using live imaging approaches, we find that strong TCR stimulation induces elevated ACD rates, and subsequent single-cell-derived colonies comprise both effector and memory precursor cells. The abundance of memory precursor cells emerging from a single activated T cell positively correlates with first mitosis ACD. Accordingly, preventing ACD by inhibition of protein kinase Cζ (PKCζ) during the first mitosis upon strong TCR stimulation markedly curtails the formation of memory precursor cells. Conversely, no effect of ACD on fate commitment is observed upon weak TCR stimulation. Our data provide relevant mechanistic insights into the role of ACD for CD8 T cell fate regulation upon different activation conditions.
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published
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Journal / series
Volume
42 (5)
Pages / Article No.
112468
Publisher
Cell Press
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Edition / version
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Date collected
Date created
Subject
asymmetric cell division; CD8 T cell differentiation; lineage tracing; single cell tracking; CD8 T cell memory; T cell receptor signaling strength; fate diversification
Organisational unit
03625 - Oxenius, Annette / Oxenius, Annette
03992 - Schroeder, Timm / Schroeder, Timm
Notes
Funding
208024 - Generation of diversity within - and regulation of - CD8 T cell responses (SNF)