PMID- 9295044
OWN - NLM
STAT- MEDLINE
DCOM- 19970930
LR  - 20181201
IS  - 0014-2980 (Print)
IS  - 0014-2980 (Linking)
VI  - 27
IP  - 8
DP  - 1997 Aug
TI  - Positive and negative thymic selection in T cell receptor-transgenic mice 
      correlate with Nur77 mRNA expression.
PG  - 2048-56
AB  - The orphan nuclear receptor Nur77 has been implicated in thymic negative 
      selection. We studied the effect of two T cell receptor (TCR) transgenes on 
      positive selection and Nur77 mRNA expression in thymus. DO11.10 mice, expressing 
      a transgenic TCR specific for an ovalbumin (OVA) 323-339 peptide presented by 
      I-Ad, were found to have an enlarged thymus with a reduced apoptotic activity, 
      measured by flow cytometry, reduced mitochondrial membrane potential and terminal 
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) techniques. 
      In contrast, in F5 mice expressing a transgenic TCR recognizing the influenza 
      virus nucleoprotein (NP) 366-374 peptide restricted by Db, this positive 
      selection effect was much less pronounced. Positive thymic selection in DO11.10 
      TCR+ mice correlated with a reduced level of Nur77 mRNA expression shown by 
      Northern blot. F5 mice expressed levels close to those expressed by the wild 
      type. Both transgenic mouse strains responded with extensive cortical apoptosis, 
      and with up-regulation of Nur77 mRNA, to injection of cognate peptides. As 
      9-cis-Retinoic acid (9-cis-RA) inhibits Nur77-dependent apoptosis in T cell 
      hybridomas in vitro, mice were pretreated with the drug to investigate a similar 
      effect in vivo. However, the drug itself, at saturating concentrations, caused 
      extensive apoptosis in immature CD4+/CD8+ thymocytes. The result demonstrates a 
      correlation between Nur77 expression and thymic apoptotic activity, both during 
      positive and negative selection events.
FAU - Xue, Y
AU  - Xue Y
AD  - Microbiology and Tumorbiology Center, Karolinska Institute, Stockholm, Sweden.
FAU - Chomez, P
AU  - Chomez P
FAU - Castanos-Velez, E
AU  - Castanos-Velez E
FAU - Biberfeld, P
AU  - Biberfeld P
FAU - Perlmann, T
AU  - Perlmann T
FAU - Jondal, M
AU  - Jondal M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Eur J Immunol
JT  - European journal of immunology
JID - 1273201
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Nr4a1 protein, mouse)
RN  - 0 (Nuclear Receptor Subfamily 4, Group A, Member 1)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Receptors, Steroid)
RN  - 0 (Transcription Factors)
RN  - 1UA8E65KDZ (Alitretinoin)
RN  - 5688UTC01R (Tretinoin)
RN  - 9006-59-1 (Ovalbumin)
SB  - IM
EIN - Eur J Immunol 1997 Oct;27(10):2748
MH  - Alitretinoin
MH  - Animals
MH  - Apoptosis/drug effects
MH  - DNA-Binding Proteins/*genetics
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Nuclear Receptor Subfamily 4, Group A, Member 1
MH  - Ovalbumin/immunology
MH  - RNA, Messenger/*genetics/*metabolism
MH  - Receptors, Antigen, T-Cell/*genetics
MH  - Receptors, Cytoplasmic and Nuclear/*genetics
MH  - Receptors, Steroid
MH  - T-Lymphocyte Subsets/cytology/drug effects/immunology
MH  - Thymus Gland/*cytology/drug effects/*immunology
MH  - Transcription Factors/*genetics
MH  - Tretinoin/pharmacology
EDAT- 1997/08/01 00:00
MHDA- 1997/09/19 00:01
CRDT- 1997/08/01 00:00
PHST- 1997/08/01 00:00 [pubmed]
PHST- 1997/09/19 00:01 [medline]
PHST- 1997/08/01 00:00 [entrez]
AID - 10.1002/eji.1830270832 [doi]
PST - ppublish
SO  - Eur J Immunol. 1997 Aug;27(8):2048-56. doi: 10.1002/eji.1830270832.