PMID- 11257136
OWN - NLM
STAT- MEDLINE
DCOM- 20010607
LR  - 20190508
IS  - 0022-1007 (Print)
IS  - 1540-9538 (Electronic)
IS  - 0022-1007 (Linking)
VI  - 193
IP  - 6
DP  - 2001 Mar 19
TI  - Evidence that gammadelta versus alphabeta T cell fate determination is initiated 
      independently of T cell receptor signaling.
PG  - 689-98
AB  - Two types of T cells, alphabeta and gammadelta, develop in vertebrates. How these 
      two T cell lineages arise from a common thymic T progenitor is poorly understood. 
      Differentiation of alphabeta lineage T cells requires the surrogate alpha chain 
      (pTalpha), which associates with the T cell receptor (TCR) beta chain to form the 
      pre-TCR. gammadelta lineage development does not appear to involve an obligatory 
      surrogate chain, but instead requires productive rearrangement and expression of 
      both TCR gamma and delta genes. It has been proposed that the quality of signals 
      transmitted by the pre-TCR and gammadelta TCR are distinct and that these 
      "instructive" signals determine the lineage fate of an uncommitted progenitor 
      cell. Here we show that the thymic T progenitor cells 
      (CD25(+)CD44(+)c-kit(+)CD3(-)CD4(-)CD8(-) thymocytes, termed pro-T cells) from 
      young adult mice that have yet to express TCRs can be subdivided based on 
      interleukin 7 receptor (IL-7R) expression. These subsets exhibit differential 
      potential to develop into gammadelta versus alphabeta lineage (CD4+CD8+ cells) in 
      the thymus. Upon intrathymic injection, IL-7R(neg-lo) pro-T cells generated a 
      13-fold higher ratio of alphabeta lineage to gammadelta lineage cells than did 
      IL-7R(+) pro-T cells. Much of this difference was due to a fivefold greater 
      potential of IL-7R(+) pro-T cells to develop into TCR-gammadelta T cells. 
      Evidence indicates that this biased developmental potential is not a result of 
      enhanced TCR-gamma gene rearrangement/expression in IL-7R(+) pro-T cells. These 
      results indicate that the pro-T cells are heterogeneous in developmental 
      potential before TCR gene rearrangement and suggest that in some precursor cells 
      the initial lineage commitment is independent of TCR-mediated signals.
FAU - Kang, J
AU  - Kang J
AD  - Department of Molecular and Cellular Biology, Cancer Research Laboratory, 
      Division of Immunology, University of California at Berkeley, Berkeley, CA 94720, 
      USA.
FAU - Volkmann, A
AU  - Volkmann A
FAU - Raulet, D H
AU  - Raulet DH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Exp Med
JT  - The Journal of experimental medicine
JID - 2985109R
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (Receptors, Antigen, T-Cell, alpha-beta)
RN  - 0 (Receptors, Antigen, T-Cell, gamma-delta)
RN  - 0 (Receptors, Interleukin-7)
SB  - IM
MH  - Animals
MH  - Cell Differentiation
MH  - Cell Lineage
MH  - Hematopoietic Stem Cells/*cytology/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Receptors, Antigen, T-Cell
MH  - *Receptors, Antigen, T-Cell, alpha-beta
MH  - *Receptors, Antigen, T-Cell, gamma-delta
MH  - Receptors, Interleukin-7/*biosynthesis
MH  - Signal Transduction/*physiology
MH  - T-Lymphocytes/*cytology/metabolism
PMC - PMC2193423
EDAT- 2001/03/21 10:00
MHDA- 2001/06/08 10:01
PMCR- 2001/09/19
CRDT- 2001/03/21 10:00
PHST- 2001/03/21 10:00 [pubmed]
PHST- 2001/06/08 10:01 [medline]
PHST- 2001/03/21 10:00 [entrez]
PHST- 2001/09/19 00:00 [pmc-release]
AID - 001716 [pii]
AID - 10.1084/jem.193.6.689 [doi]
PST - ppublish
SO  - J Exp Med. 2001 Mar 19;193(6):689-98. doi: 10.1084/jem.193.6.689.