CD8+T Lymphocyte Self-Renewal during Effector Cell Determination.
Selected CD8+T cells must divide, produce differentiated effector cells, and self-renew, often repeatedly. We now show that silencing expression of the transcription factor TCF1 marks loss of self-renewal by determined effector cells and that this requires cell division. In acute infections, the first three CD8+T cell divisions produce daughter cells with unequal proliferative signaling but uniform maintenance of TCF1 expression. The more quiescent initial daughter cells resemble canonical central memory cells. The more proliferative, effector-prone cells from initial divisions can subsequently undergo division-dependent production of a TCF1-negative effector daughter cell along with a self-renewing TCF1-positive daughter cell, the latter also contributing to the memory cell pool upon resolution of infection. Self-renewal in the face of effector cell determination may promote clonal amplification and memory cell formation in acute infections, sustain effector regeneration during persistent subclinical infections, and be rate limiting, but remediable, in chronic active infections and cancer.
Department of Microbiology and Immunology and Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Wen-Hsuan W
WW
Lin
Department of Microbiology and Immunology and Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Simone A
SA
Nish
Department of Microbiology and Immunology and Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Bonnie
B
Yen
Department of Microbiology and Immunology and Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Yen-Hua
YH
Chen
Department of Microbiology and Immunology and Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
William C
WC
Adams
Department of Microbiology and Immunology and Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Radomir
R
Kratchmarov
Department of Microbiology and Immunology and Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Nyanza J
NJ
Rothman
T-Cell Biology and Development Unit, Laboratory of Genome Integrity, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Avinash
A
Bhandoola
Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
Hai-Hui
HH
Xue
Department of Microbiology and Immunology and Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. Electronic address: sr2978@cumc.columbia.edu.
Steven L
SL
Reiner
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D002453:Cell Cycle; D002454:Cell Differentiation; D002455:Cell Division; D049109:Cell Proliferation; D000066673:Cell Self Renewal; D002999:Clone Cells; D020868:Gene Silencing; D008810:Mice, Inbred C57BL; D051822:T Cell Transcription Factor 1 / Q000378:metabolism
D051822:T Cell Transcription Factor 1
T cell; TCF1; Tcf7; asymmetric division; lymphocyte; memory; metabolism; progenitor; self-renewal; stem cell