TCF1 expression marks self-renewing human CD8+ T cells

R Kratchmarov, AM Magun, SL Reiner - Blood advances, 2018 - ashpublications.org
R Kratchmarov, AM Magun, SL Reiner
Blood advances, 2018ashpublications.org
Expression of the transcription factor T-cell factor 1 (TCF1) identifies antigen-experienced
murine CD8+ T cells that retain potential for lymphoid recirculation and the ability to self-
renew while producing more differentiated effector cells. We found that CD8+ T cells in the
blood of both healthy and chronically infected humans expressed TCF1 at 3 distinct levels:
high (TCF1-hi), intermediate (TCF1-int), and low (TCF1-lo). TCF1-hi cells could be found
within both the naive and memory compartments and were characterized by relative …
Abstract
Expression of the transcription factor T-cell factor 1 (TCF1) identifies antigen-experienced murine CD8+ T cells that retain potential for lymphoid recirculation and the ability to self-renew while producing more differentiated effector cells. We found that CD8+ T cells in the blood of both healthy and chronically infected humans expressed TCF1 at 3 distinct levels: high (TCF1-hi), intermediate (TCF1-int), and low (TCF1-lo). TCF1-hi cells could be found within both the naive and memory compartments and were characterized by relative quiescence and lack of immediate effector function. A substantial fraction of TCF1-int cells were found among memory cells, and TCF1-int cells exhibited robust immediate effector functions. TCF1-lo cells were most enriched in effector memory cells that expressed the senescence marker CD57. Following reactivation, TCF1-hi cells gave rise to TCF1-lo descendants while self-renewing the TCF1-hi progenitor. By contrast, reactivation of TCF1-lo cells produced more TCF1-lo cells without evidence of de-differentiating into TCF1-hi cells. Flow cytometric analyses of TCF1 expression from patient specimens may become a useful biomarker for adaptive immune function in response to vaccination, infection, autoimmunity, and cancer.
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