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Notch induces human T-cell receptor γδ+ thymocytes to differentiate along a parallel, highly proliferative and bipotent CD4 CD8 double-positive pathway

Van Coppernolle, Stefanie UGent, Vanhee, Stijn, Verstichel, Greet UGent, SNAUWAERT, SYLVIA, van der Spek, A, Velghe, Imke UGent, Sinnesael, Mieke UGent, Heemskerk, MH, Taghon, Tom UGent, Leclercq, Georges UGent, et al. (2012) LEUKEMIA. 26(1). p.127-138
abstract
In wild-type mice, T-cell receptor (TCR) gamma delta(+) cells differentiate along a CD4 CD8 double-negative (DN) pathway whereas TCR alpha beta(+) cells differentiate along the double-positive (DP) pathway. In the human postnatal thymus (PNT), DN, DP and single-positive (SP) TCR gamma delta(+) populations are present. Here, the precursor-progeny relationship of the various PNT TCR gamma delta(+) populations was studied and the role of the DP TCR gamma delta(+) population during T-cell differentiation was elucidated. We demonstrate that human TCR gamma delta(+) cells differentiate along two pathways downstream from an immature CD1(+) DN TCR gamma delta(+) precursor: a Notch-independent DN pathway generating mature DN and CD8 alpha alpha SP TCR gamma delta(+) cells, and a Notch-dependent, highly proliferative DP pathway generating immature CD4 SP and subsequently DP TCR gamma delta(+) populations. DP TCR gamma delta(+) cells are actively rearranging the TCR alpha locus, and differentiate to TCR- DP cells, to CD8 alpha beta SP TCR gamma delta(+) cells and to TCR alpha beta(+) cells. Finally, we show that the gamma delta subset of T-cell acute lymphoblastic leukemias (T-ALL) consists mainly of CD4 SP or DP phenotypes carrying significantly more activating Notch mutations than DN T-ALL. The latter suggests that activating Notch mutations in TCR gamma delta(+) thymocytes induce proliferation and differentiation along the DP pathway in vivo.
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author
organization
alternative title
Notch induces human T-cell receptor gamma delta plus thymocytes to differentiate along a parallel, highly proliferative and bipotent CD4 CD8 double-positive pathway
year
type
journalArticle (original)
publication status
published
subject
keyword
ACTIVATION, IMMUNOGLOBULIN, REARRANGEMENTS, BETA-LINEAGE, FATE, EXPRESSION, FUNCTIONAL MATURATION, LINEAGE COMMITMENT, ALPHA-BETA/GAMMA-DELTA, gammadelta T-cell, ACUTE LYMPHOBLASTIC-LEUKEMIA, thymus, Notch
journal title
LEUKEMIA
Leukemia
volume
26
issue
1
pages
127 - 138
Web of Science type
Article
Web of Science id
000299317400013
JCR category
HEMATOLOGY
JCR impact factor
10.164 (2012)
JCR rank
2/66 (2012)
JCR quartile
1 (2012)
ISSN
0887-6924
DOI
10.1038/leu.2011.324
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
2026843
handle
http://hdl.handle.net/1854/LU-2026843
date created
2012-02-10 12:03:29
date last changed
2016-12-19 15:46:06
@article{2026843,
  abstract     = {In wild-type mice, T-cell receptor (TCR) gamma delta(+) cells differentiate along a CD4 CD8 double-negative (DN) pathway whereas TCR alpha beta(+) cells differentiate along the double-positive (DP) pathway. In the human postnatal thymus (PNT), DN, DP and single-positive (SP) TCR gamma delta(+) populations are present. Here, the precursor-progeny relationship of the various PNT TCR gamma delta(+) populations was studied and the role of the DP TCR gamma delta(+) population during T-cell differentiation was elucidated. We demonstrate that human TCR gamma delta(+) cells differentiate along two pathways downstream from an immature CD1(+) DN TCR gamma delta(+) precursor: a Notch-independent DN pathway generating mature DN and CD8 alpha alpha SP TCR gamma delta(+) cells, and a Notch-dependent, highly proliferative DP pathway generating immature CD4 SP and subsequently DP TCR gamma delta(+) populations. DP TCR gamma delta(+) cells are actively rearranging the TCR alpha locus, and differentiate to TCR- DP cells, to CD8 alpha beta SP TCR gamma delta(+) cells and to TCR alpha beta(+) cells. Finally, we show that the gamma delta subset of T-cell acute lymphoblastic leukemias (T-ALL) consists mainly of CD4 SP or DP phenotypes carrying significantly more activating Notch mutations than DN T-ALL. The latter suggests that activating Notch mutations in TCR gamma delta(+) thymocytes induce proliferation and differentiation along the DP pathway in vivo.},
  author       = {Van Coppernolle, Stefanie and Vanhee, Stijn and Verstichel, Greet and SNAUWAERT, SYLVIA and van der Spek, A and Velghe, Imke and Sinnesael, Mieke and Heemskerk, MH and Taghon, Tom and Leclercq, Georges and Plum, Jean and Langerak, AW and Kerre, Tessa and Vandekerckhove, Bart},
  issn         = {0887-6924},
  journal      = {LEUKEMIA},
  keyword      = {ACTIVATION,IMMUNOGLOBULIN,REARRANGEMENTS,BETA-LINEAGE,FATE,EXPRESSION,FUNCTIONAL MATURATION,LINEAGE COMMITMENT,ALPHA-BETA/GAMMA-DELTA,gammadelta T-cell,ACUTE LYMPHOBLASTIC-LEUKEMIA,thymus,Notch},
  language     = {eng},
  number       = {1},
  pages        = {127--138},
  title        = {Notch induces human T-cell receptor \ensuremath{\gamma}\ensuremath{\delta}+ thymocytes to differentiate along a parallel, highly proliferative and bipotent CD4 CD8 double-positive pathway},
  url          = {http://dx.doi.org/10.1038/leu.2011.324},
  volume       = {26},
  year         = {2012},
}

Chicago
Van Coppernolle, Stefanie, Stijn Vanhee, Greet Verstichel, SYLVIA SNAUWAERT, A van der Spek, Imke Velghe, Mieke Sinnesael, et al. 2012. “Notch Induces Human T-cell Receptor Γδ+ Thymocytes to Differentiate Along a Parallel, Highly Proliferative and Bipotent CD4 CD8 Double-positive Pathway.” Leukemia 26 (1): 127–138.
APA
Van Coppernolle, S., Vanhee, S., Verstichel, G., SNAUWAERT, S., van der Spek, A., Velghe, I., Sinnesael, M., et al. (2012). Notch induces human T-cell receptor γδ+ thymocytes to differentiate along a parallel, highly proliferative and bipotent CD4 CD8 double-positive pathway. LEUKEMIA, 26(1), 127–138.
Vancouver
1.
Van Coppernolle S, Vanhee S, Verstichel G, SNAUWAERT S, van der Spek A, Velghe I, et al. Notch induces human T-cell receptor γδ+ thymocytes to differentiate along a parallel, highly proliferative and bipotent CD4 CD8 double-positive pathway. LEUKEMIA. 2012;26(1):127–38.
MLA
Van Coppernolle, Stefanie, Stijn Vanhee, Greet Verstichel, et al. “Notch Induces Human T-cell Receptor Γδ+ Thymocytes to Differentiate Along a Parallel, Highly Proliferative and Bipotent CD4 CD8 Double-positive Pathway.” LEUKEMIA 26.1 (2012): 127–138. Print.