RT Journal Article
SR Electronic
T1 Latent Plasticity of Effector-like Exhausted CD8 T cells contributes to memory responses
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.02.22.960278
DO 10.1101/2020.02.22.960278
A1 Saravanan Raju
A1 Yu Xia
A1 Bence Daniel
A1 Kathryn E. Yost
A1 Elliot Bradshaw
A1 Elena Tonc
A1 Daniel J. Verbaro
A1 Ansuman T. Satpathy
A1 Takeshi Egawa
YR 2020
UL http://biorxiv.org/content/early/2020/02/25/2020.02.22.960278.abstract
AB Persistent antigen induces a dysfunctional CD8 T cell state known as T cell “exhaustion” characterized by expression of PD-1 and decreased effector functions 1–3. Nevertheless, dysfunctional CD8 T cells can mediate control of antigen burden which is long-lasting. While significant heterogeneity of exhausted CD8 T cells has been described, the cells which actively proliferate and exert direct viral control have remained elusive. Here, we define subsets of PD-1+ CD8 T cells marked by expression of CX3CR1 exhibit substantial in situ proliferation and expression of granzyme B during chronic infection for the maintenance of the effector pool through self-renewal independently of previously defined stem-like cells. Unexpectedly, the CX3CR1+ CD8 T cells retain plasticity to be reprogrammed to memory cells through expression of TCF-1 and re-gain polyfunctionality. Thus, we define a subset of effector-like exhausted CD8 T cells with capacity to contribute to the memory pool, offering a prime target for novel immunotherapies.