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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

Stefanie Van Coppernolle (UGent) , Stijn Vanhee (UGent) , Greet Verstichel (UGent) , SYLVIA SNAUWAERT (UGent) , A van der Spek, Imke Velghe (UGent) , Mieke Sinnesael (UGent) , MH Heemskerk, Tom Taghon (UGent) , Georges Leclercq (UGent) , et al.
(2012) LEUKEMIA. 26(1). p.127-138
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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.
Keywords
ACTIVATION, IMMUNOGLOBULIN, REARRANGEMENTS, BETA-LINEAGE, FATE, EXPRESSION, FUNCTIONAL MATURATION, LINEAGE COMMITMENT, ALPHA-BETA/GAMMA-DELTA, gammadelta T-cell, ACUTE LYMPHOBLASTIC-LEUKEMIA, thymus, Notch

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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.
@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},
  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},
}

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