Journal
BLOOD ADVANCES
Volume 2, Issue 14, Pages 1685-1690Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/bloodadvances.2018016279
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Funding
- National Institutes of Health, National Institute of Allergy and Infectious Diseases [AI113365, AI076458]
- Charles H. Revson Foundation
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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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