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Journal Articles Science Immunology Year : 2021

Inhibitory signaling sustains a distinct early memory CD8 + T cell precursor that is resistant to DNA damage

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Avinash Bhandoola

Abstract

The developmental origins of memory T cells remain incompletely understood. During the expansion phase of acute viral infection, we identified a distinct subset of virus-specific CD8 + T cells that possessed distinct characteristics including expression of CD62L, T cell factor 1 (TCF-1), and Eomesodermin; relative quiescence; expression of activation markers; and features of limited effector differentiation. These cells were a quantitatively minor subpopulation of the TCF-1 + pool and exhibited self-renewal, heightened DNA damage surveillance activity, and preferential long-term recall capacity. Despite features of memory and somewhat restrained proliferation during the expansion phase, this subset displayed evidence of stronger TCR signaling than other responding CD8 + T cells, coupled with elevated expression of multiple inhibitory receptors including programmed cell death 1 (PD-1), lymphocyte activating gene 3 (LAG-3), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), CD5, and CD160. Genetic ablation of PD-1 and LAG-3 compromised the formation of this CD62L hi TCF-1 + subset and subsequent CD8 + T cell memory. Although central memory phenotype CD8 + T cells were formed in the absence of these cells, subsequent memory CD8 + T cell recall responses were compromised. Together, these results identify an impor tant link between genome integrity maintenance and CD8 + T cell memory. Moreover, the data indicate a role for inhibitory receptors in preserving key memory CD8 + T cell precursors during initial activation and differentiation. Identification of this rare subpopulation within the memory CD8 + T cell precursor pool may help reconcile models of the developmental origin of long-term CD8 + T cell memory.
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Dates and versions

inserm-03276330 , version 1 (02-07-2021)

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Jonathan B Johnnidis, Yuki Muroyama, Shin Foong Ngiow, Zeyu Chen, Sasikanth Manne, et al.. Inhibitory signaling sustains a distinct early memory CD8 + T cell precursor that is resistant to DNA damage. Science Immunology, 2021, 6, pp.eabe3702. ⟨10.1126/sciimmunol.abe3702⟩. ⟨inserm-03276330⟩
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