TY - JOUR
T1 - One naive T cell, multiple fates in CD8+ T cell differentiation
AU - Gerlach, Carmen
AU - van Heijst, Jeroen W J
AU - Swart, Erwin
AU - Sie, Daoud
AU - Armstrong, Nicola
AU - Kerkhoven, Ron M
AU - Zehn, Dietmar
AU - Bevan, Michael J
AU - Schepers, Koen
AU - Schumacher, Ton N M
PY - 2010/6/7
Y1 - 2010/6/7
N2 - The mechanism by which the immune system produces effector and memory T cells is largely unclear. To allow a large-scale assessment of the development of single naive T cells into different subsets, we have developed a technology that introduces unique genetic tags (barcodes) into naive T cells. By comparing the barcodes present in antigen-specific effector and memory T cell populations in systemic and local infection models, at different anatomical sites, and for TCR-pMHC interactions of different avidities, we demonstrate that under all conditions tested, individual naive T cells yield both effector and memory CD8+ T cell progeny. This indicates that effector and memory fate decisions are not determined by the nature of the priming antigen-presenting cell or the time of T cell priming. Instead, for both low and high avidity T cells, individual naive T cells have multiple fates and can differentiate into effector and memory T cell subsets.
AB - The mechanism by which the immune system produces effector and memory T cells is largely unclear. To allow a large-scale assessment of the development of single naive T cells into different subsets, we have developed a technology that introduces unique genetic tags (barcodes) into naive T cells. By comparing the barcodes present in antigen-specific effector and memory T cell populations in systemic and local infection models, at different anatomical sites, and for TCR-pMHC interactions of different avidities, we demonstrate that under all conditions tested, individual naive T cells yield both effector and memory CD8+ T cell progeny. This indicates that effector and memory fate decisions are not determined by the nature of the priming antigen-presenting cell or the time of T cell priming. Instead, for both low and high avidity T cells, individual naive T cells have multiple fates and can differentiate into effector and memory T cell subsets.
KW - Animals
KW - CD8-Positive T-Lymphocytes/cytology
KW - Cell Differentiation/immunology
KW - Cell Lineage/immunology
KW - Immunologic Memory/immunology
KW - Listeriosis/complications
KW - Lymphoid Tissue/cytology
KW - Mice
KW - Mice, Inbred C57BL
KW - Orthomyxoviridae Infections/complications
KW - Receptors, Antigen, T-Cell/immunology
KW - T-Lymphocyte Subsets/cytology
U2 - 10.1084/jem.20091175
DO - 10.1084/jem.20091175
M3 - Article
C2 - 20479114
VL - 207
SP - 1235
EP - 1246
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 6
ER -