TY - JOUR
T1 - Attenuation of gammadeltaTCR signaling efficiently diverts thymocytes to the alphabeta lineage
AU - Haks, Mariëlle C
AU - Lefebvre, Juliette M
AU - Lauritsen, Jens Peter H
AU - Carleton, Michael
AU - Rhodes, Michele
AU - Miyazaki, Toru
AU - Kappes, Dietmar J
AU - Wiest, David L
N1 - Keywords: Animals; Cell Differentiation; DNA-Binding Proteins; Early Growth Response Protein 1; Extracellular Signal-Regulated MAP Kinases; Immediate-Early Proteins; Inhibitor of Differentiation Proteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Phosphorylation; Proteins; Receptors, Antigen, T-Cell, alpha-beta; Receptors, Antigen, T-Cell, gamma-delta; Signal Transduction; T-Lymphocyte Subsets; Transcription Factors
PY - 2005
Y1 - 2005
N2 - The role of the T cell antigen receptor complex (TCR) in alphabeta/gammadelta lineage commitment remains controversial, in particular whether different TCR isoforms intrinsically favor adoption of a certain lineage. Here, we demonstrate that impairing the signaling capacity of a gammadeltaTCR complex enables it to efficiently direct thymocytes to the alphabeta lineage. In the presence of a ligand, a transgenic gammadeltaTCR mediates almost exclusive adoption of the gammadelta lineage, while in the absence of ligand, the same gammadeltaTCR promotes alphabeta lineage development with efficiency comparable to the pre-TCR. Importantly, attenuating gammadeltaTCR signaling through Lck deficiency causes reduced ERK1/2 activation and Egr expression and diverts thymocytes to the alphabeta lineage even in the presence of ligand. Conversely, ectopic Egr overexpression favors gammadelta T cell development. Our data support a model whereby gammadelta versus alphabeta lineage commitment is controlled by TCR signal strength, which depends critically on the ERK MAPK-Egr pathway.
AB - The role of the T cell antigen receptor complex (TCR) in alphabeta/gammadelta lineage commitment remains controversial, in particular whether different TCR isoforms intrinsically favor adoption of a certain lineage. Here, we demonstrate that impairing the signaling capacity of a gammadeltaTCR complex enables it to efficiently direct thymocytes to the alphabeta lineage. In the presence of a ligand, a transgenic gammadeltaTCR mediates almost exclusive adoption of the gammadelta lineage, while in the absence of ligand, the same gammadeltaTCR promotes alphabeta lineage development with efficiency comparable to the pre-TCR. Importantly, attenuating gammadeltaTCR signaling through Lck deficiency causes reduced ERK1/2 activation and Egr expression and diverts thymocytes to the alphabeta lineage even in the presence of ligand. Conversely, ectopic Egr overexpression favors gammadelta T cell development. Our data support a model whereby gammadelta versus alphabeta lineage commitment is controlled by TCR signal strength, which depends critically on the ERK MAPK-Egr pathway.
U2 - 10.1016/j.immuni.2005.04.003
DO - 10.1016/j.immuni.2005.04.003
M3 - Journal article
C2 - 15894277
SN - 1074-7613
VL - 22
SP - 595
EP - 606
JO - Immunity
JF - Immunity
IS - 5
ER -