RT Journal Article
SR Electronic
T1 TCF-1 regulates the stem-like memory potential of HIV-specific CD8+ T cells in elite controllers
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.01.07.894535
DO 10.1101/2020.01.07.894535
A1 Rachel L. Rutishauser
A1 Christian Deo T. Deguit
A1 Joseph Hiatt
A1 Franziska Blaeschke
A1 Theodore L. Roth
A1 Lynn Wang
A1 Kyle Raymond
A1 Carly E. Starke
A1 Joseph C. Mudd
A1 Wenxuan Chen
A1 Carolyn Smullin
A1 Rodrigo Matus-Nicodemos
A1 Rebecca Hoh
A1 Melissa Krone
A1 Frederick M. Hecht
A1 Christopher D. Pilcher
A1 Jeffrey N. Martin
A1 Richard A. Koup
A1 Daniel C. Douek
A1 Jason M. Brenchley
A1 Rafick-Pierre Sékaly
A1 Satish K. Pillai
A1 Alexander Marson
A1 Steven G. Deeks
A1 Joseph M. McCune
A1 Peter W. Hunt
YR 2020
UL http://biorxiv.org/content/early/2020/01/08/2020.01.07.894535.abstract
AB Although many HIV cure strategies seek to expand HIV-specific CD8+ T cells to control the virus, all are likely to fail if cellular exhaustion is not prevented. A loss in stem-like memory properties (i.e., the ability to proliferate and generate secondary effector cells) is a key feature of exhaustion; little is known, however, about how these properties are regulated in human virus-specific CD8+ T cells. We found that virus-specific CD8+ T cells from humans and non-human primates naturally controlling HIV/SIV infection express more of the transcription factor, TCF-1, than non-controllers. HIV-specific CD8+ T cell TCF-1 expression correlated with memory marker expression and proliferative capacity and declined with antigenic stimulation. CRISPR-Cas9 editing of TCF-1 in human primary T cells demonstrated a direct role in regulating expansion capacity. Collectively, these data suggest that TCF-1 controls the stem-like memory properties of HIV-specific CD8+ T cells and provides a rationale for enhancing this pathway in T cell-based therapeutic strategies for HIV.One Sentence Summary TCF-1 is highly expressed in HIV-specific CD8+ T cells from elite controllers and directly regulates human CD8+ T cell expansion capacity in response to T cell receptor stimulation.