PMID- 9243099
OWN - NLM
STAT- MEDLINE
DCOM- 19971015
LR  - 20081121
IS  - 0012-186X (Print)
IS  - 0012-186X (Linking)
VI  - 40
IP  - 7
DP  - 1997 Jul
TI  - The lymphopenia (lyp) gene controls the intrathymic cytokine ratio in congenic 
      BioBreeding rats.
PG  - 786-92
AB  - The lymphopenia gene (lyp) on rat chromosome 4 is closely linked to autoimmune 
      diabetes in the BioBreeding (BB) rat. Lyp controls the number of peripheral 
      lymphocytes by reducing T cells of the RT6+ phenotype by almost 90%. Following 
      nine cycle of marker-assisted cross-intercross breeding we have developed 
      congenic lyp/lyp, lyp/+ and +/+ (wildtype) rats on the background of DR rats. 
      Prediabetic and insulitis free lyp/lyp, lyp/+ and +/+ rats were used to determine 
      the effect of lyp on cytokine expression in the thymus. In situ hybridization of 
      thymus cryosections showed that the interferon gamma (IFN gamma) mRNA expression 
      was highest in lyp/lyp rats and the hybridization signal was restricted to the 
      medullary compartment. The frequency of IFN gamma and interleukin (IL)-10 mRNA 
      expressing cells in isolated thymocytes determined by quantitative image 
      analysis, demonstrated an increased IFN gamma: IL-10 ratio in thymocytes from 
      lyp/lyp homozygotes compared to lyp/+ and +/+ rats. This confirmed a lyp gene 
      dose-dependent segregation of the IFN gamma high phenotype. Recombinant human 
      glutamic acid decarboxylase (GAD65) increased the number of IFN gamma and IL-10 
      mRNA expressing thymocytes after in vitro culture. We conclude that the 
      quantitative ratio of cytokine producing thymocytes is associated with the lyp 
      genotype. These potentially autoreactive thymocytes may explain the establishment 
      of beta-cell directed autoimmunity in the BB rat despite peripheral lymphopenia.
FAU - Bieg, S
AU  - Bieg S
AD  - Department of Medicine, Robert H. Williams Laboratory, University of Washington, 
      Seattle 98195-7710, USA.
FAU - Moller, C
AU  - Moller C
FAU - Olsson, T
AU  - Olsson T
FAU - Lernmark, A
AU  - Lernmark A
LA  - eng
SI  - GENBANK/M29315
SI  - GENBANK/M29316
SI  - GENBANK/M29317
SI  - GENBANK/M37897
GR  - DK 46620/DK/NIDDK 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.
PL  - Germany
TA  - Diabetologia
JT  - Diabetologia
JID - 0006777
RN  - 0 (Cytokines)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Proteins)
RN  - 130068-27-8 (Interleukin-10)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 4.1.1.15 (Glutamate Decarboxylase)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Cytokines/*biosynthesis
MH  - Glutamate Decarboxylase/pharmacology
MH  - Homozygote
MH  - Humans
MH  - Interferon-gamma/biosynthesis
MH  - Interleukin-10/biosynthesis
MH  - Lymphopenia/*genetics/immunology
MH  - Molecular Sequence Data
MH  - RNA, Messenger/biosynthesis
MH  - Rats
MH  - Rats, Inbred BB
MH  - Recombinant Proteins/pharmacology
MH  - T-Lymphocytes/drug effects/*immunology
MH  - Thymus Gland/*immunology
MH  - *Transcription, Genetic
EDAT- 1997/07/01 00:00
MHDA- 1997/07/01 00:01
CRDT- 1997/07/01 00:00
PHST- 1997/07/01 00:00 [pubmed]
PHST- 1997/07/01 00:01 [medline]
PHST- 1997/07/01 00:00 [entrez]
AID - 10.1007/s001250050750 [doi]
PST - ppublish
SO  - Diabetologia. 1997 Jul;40(7):786-92. doi: 10.1007/s001250050750.