Identification of a t-bethi quiescent exhausted cd8 t cell subpopulation that can differentiate into tim3+cx3cr1+ effectors and memory-like cells

Saravanan Raju, Yu Xia, Bence Daniel, Kathryn E. Yost, Elliot Bradshaw, Elena Tonc, Daniel J. Verbaro, Kohei Kometani, Wayne M. Yokoyama, Tomohiro Kurosaki, Ansuman T. Satpathy, Takeshi Egawa

Research output: Contribution to journalArticlepeer-review

Abstract

Persistent Ag induces a dysfunctional CD8 T cell state known as "exhaustion"characterized by PD-1 expression. Nevertheless, exhausted CD8 T cells retain functionality through continued differentiation of progenitor into effector cells. However, it remains ill-defined how CD8 T cell effector responses are sustained in situ. In this study, we show using the mouse chronic lymphocytic choriomeningitis virus infection model that CX3CR1+ CD8 T cells contain a T-bet-dependent TIM3_PD-1lo subpopulation that is distinct from the TIM3+CX3CR1+PD-1+ proliferative effector subset. The TIM3_CX3CR1+ cells are quiescent and express a low but significant level of the transcription factor TCF-1, demonstrating similarity to TCF-1hi progenitor CD8 T cells. Furthermore, following the resolution of lymphocytic choriomeningitis virus viremia, a substantial proportion of TCF-1+ memory-like CD8 T cells show evidence of CX3CR1 expression during the chronic phase of the infection. Our results suggest a subset of the CX3CR1+ exhausted population demonstrates progenitor-like features that support the generation of the CX3CR1+ effector pool from the TCF-1hi progenitors and contribute to the memory-like pool following the resolution of viremia.

Original languageEnglish
Pages (from-to)2924-2936
Number of pages13
JournalJournal of Immunology
Volume206
Issue number12
DOIs
StatePublished - Jun 15 2021

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