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
2006 (English)In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 55, no 2, 538-544 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2006. Vol. 55, no 2, 538-544 p.
Alleles, Animals, Antigens; CD, Antigens; Differentiation/genetics/*metabolism, Cells; Cultured, Chromosomes; Mammalian/*genetics, Diabetes Mellitus/*genetics, Female, Gene Expression Regulation, Genetic Predisposition to Disease, Genotype, Interleukin-2/*genetics, Mice, Mice; Inbred C57BL, Mice; Inbred NOD, Physical Chromosome Mapping, Spleen/cytology, Telomere/*genetics
Immunology in the medical area
IdentifiersURN: urn:nbn:se:umu:diva-15296DOI: 10.2337/diabetes.55.02.06.db05-1240ISI: 000235178400037PubMedID: 16443792ScopusID: 2-s2.0-33644753940OAI: oai:DiVA.org:umu-15296DiVA: diva2:154968