Defective Induction of CTLA-4 in the NOD Mouse Is Controlled by the NOD Allele of Idd3/IL-2 and a Novel Locus (Ctex) Telomeric on Chromosome 1
Defective Induction of CTLA-4 in the NOD Mouse Is Controlled by the NOD Allele of Idd3/IL-2 and a Novel Locus ( Ctex ) Telomeric on Chromosome 1 Marie Lundholm , Vinicius Motta , Anna Löfgren-Burström , Nadia Duarte , Marie-Louise Bergman , Sofia Mayans and Dan Holmberg From the Department of Medica...
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Published in | Diabetes (New York, N.Y.) Vol. 55; no. 2; pp. 538 - 544 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Alexandria, VA
American Diabetes Association
01.02.2006
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Subjects | |
Online Access | Get full text |
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Summary: | Defective Induction of CTLA-4 in the NOD Mouse Is Controlled by the NOD Allele of Idd3/IL-2 and a Novel Locus ( Ctex ) Telomeric on Chromosome 1
Marie Lundholm ,
Vinicius Motta ,
Anna Löfgren-Burström ,
Nadia Duarte ,
Marie-Louise Bergman ,
Sofia Mayans and
Dan Holmberg
From the Department of Medical Biosciences, Division of Clinical and Medical Genetics, Umeå University, Umeå, Sweden
Address correspondence and reprint requests to Dr. Dan Holmberg, Department of Medical Biosciences, Division of Medical and
Clinical Genetics, Umeå University, S-901 85 Umeå, Sweden. E-mail: dan.holmberg{at}medbio.umu.se
Abstract
Cytotoxic T-lymphocyte–associated antigen-4 (CTLA-4), or CD152, is a negative regulator of T-cell activation and has been
shown to be associated with autoimmune diseases. Previous work has demonstrated a defect in the expression of this molecule
in nonobese diabetic (NOD) mice upon anti-CD3 stimulation in vitro. Using a genetic approach we here demonstrate that a novel
locus (Ctex) telomeric on chromosome 1 together with the Idd3 ( Il-2 ) gene confers optimal CTLA-4 expression upon CD3 activation of T-cells. Based on these data, we provide a model for how gene
interaction between Idd3 ( IL-2 ), Ctex , and Idd5.1 ( Ctla-4 ) could confer susceptibility to autoimmune diabetes in the NOD mouse. Additionally, we showed that the Ctex and the Idd3 regions do not influence inducible T-cell costimulator (ICOS) protein expression in NOD mice. Instead, as previously shown,
higher ICOS levels in NOD mice appear to be controlled by gene(s) in the Idd5.1 region, possibly a polymorphism in the Icos gene itself.
APC, allophycocyanin
CTLA-4, cytotoxic T-lymphocyte–associated antigen 4
FITC, fluorescein isothiocyanate
ICOS, inducible T-cell costimulator
IL, interleukin
LOD, logarithm of odds
mAb, monoclonal antibody
PE, phycoerythrin
TCR, T-cell receptor
QTL, quantitative trait locus
Footnotes
M.L. and V.M. contributed equally to this work.
Accepted November 9, 2005.
Received September 22, 2005.
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0012-1797 1939-327X 1939-327X |
DOI: | 10.2337/diabetes.55.02.06.db05-1240 |