PMID- 14592827
OWN - NLM
STAT- MEDLINE
DCOM- 20040415
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 103
IP  - 6
DP  - 2004 Mar 15
TI  - Overexpression of IL-7R alpha provides a competitive advantage during early 
      T-cell development.
PG  - 1985-94
AB  - Critical checkpoints controlling early thymic T-cell development and homeostasis 
      are set by the proper signaling function of the interleukin 7 receptor (IL-7R) 
      and the pre-T-cell antigen receptor. Although alpha beta T-cell development is 
      observed in IL-7- and IL-7R alpha-deficient mice, the number of thymocytes is 
      significantly reduced, implying a role for the IL-7R in controlling the size of 
      the thymic T-cell compartment. Here, we report the overexpression of IL-7R alpha 
      that occurs in the early T-cell compartment from AKR/J mice, animals that are 
      highly susceptible to the spontaneous development of thymoma. Increased IL-7R 
      alpha was revealed by surface staining, and increased IL-7R alpha mRNA was 
      documented by using reverse transcriptase-polymerase chain reaction (RT-PCR). 
      This resulted in increased survival of AKR/J early thymocytes, shown by the 
      decreased frequency of TUNEL(+) (terminal deoxynucleotidyl transferase mediated 
      deoxyuridine triphosphate [dUTP]-fluorescein nick end labeling) cells. In an in 
      vivo thymocyte repopulation model, AKR/J thymocytes had a selective advantage 
      over healthy thymocytes. This advantage occurred at early stages of T-cell 
      development. Our findings support the model that overexpression of growth factor 
      receptors can contribute to proliferation and malignancy.
FAU - Laouar, Yasmina
AU  - Laouar Y
AD  - Section of Immunobiology, Yale University School of Medicine, 300 Ceda St, CAB 
      S-569, New Haven, CT 06520, USA. richard.flavell@yale.edu
FAU - Crispe, I Nicholas
AU  - Crispe IN
FAU - Flavell, Richard A
AU  - Flavell RA
LA  - eng
GR  - GM56689/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20031030
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Receptors, Interleukin-7)
RN  - 0 (interleukin-7 receptor, alpha chain)
SB  - IM
MH  - Animals
MH  - Cell Survival/immunology
MH  - Gene Expression Regulation, Developmental
MH  - Gene Expression Regulation, Neoplastic
MH  - Immune System/embryology/*physiopathology
MH  - Leukemia/physiopathology
MH  - Mice
MH  - Mice, Inbred AKR
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred CBA
MH  - Mice, Mutant Strains
MH  - Receptors, Interleukin-7/*genetics
MH  - Regeneration/immunology
MH  - T-Lymphocytes/cytology/*physiology
MH  - Thymoma/*physiopathology
MH  - Thymus Neoplasms/*physiopathology
EDAT- 2003/11/01 05:00
MHDA- 2004/04/16 05:00
CRDT- 2003/11/01 05:00
PHST- 2003/11/01 05:00 [pubmed]
PHST- 2004/04/16 05:00 [medline]
PHST- 2003/11/01 05:00 [entrez]
AID - S0006-4971(20)49987-2 [pii]
AID - 10.1182/blood-2003-06-2126 [doi]
PST - ppublish
SO  - Blood. 2004 Mar 15;103(6):1985-94. doi: 10.1182/blood-2003-06-2126. Epub 2003 Oct 
      30.