CTLA-4-/- mice display T cell-apoptosis resistance resembling that ascribed to autoimmune-prone non-obese diabetic (NOD) mice. 2001

M L Bergman, and C M Cilio, and C Penha-Gonçalves, and S E Lamhamedi-Cherradi, and A Löfgren, and F Colucci, and K Lejon, and H J Garchon, and D Holmberg
Department of Cell and Molecular Biology, University of Umeå, S-901 87 Umeå Sweden.

The genes conferring susceptibility to autoimmune (insulin-dependent) diabetes mellitus (IDDM) are, in most cases, not defined. Among the loci so far identified as associated with murine IDDM (Idd1-19), only the nature of Idd1 has been assessed. Here we show that thymocytes and peripheral lymphocytes of the non-obese diabetic (NOD) mouse are relatively resistant to apoptosis induced by gamma-irradiation. By linkage analysis of F2 progeny mice, we map this trait to a locus on chromosome 1 containing the Idd5 diabetes susceptibility region. By the use of congenic mice, we confirm the linkage data and map this locus to a 6 cM region on proximal chromosome 1. Ctla4, being localized in this chromosomal region and mediating crucial functions in T cell biology, is a logical candidate gene in the Idd5 susceptibility region. In line with this, we demonstrate that T cells from Ctla4(-/-)deficient mice show a similar resistance to gamma-irradiation-induced apoptosis as observed in the NOD mice. This reinforces the notion that CTLA-4 contributes to the pathogenesis of autoimmune diabetes.

UI MeSH Term Description Entries
D011836 Radiation Tolerance The ability of some cells or tissues to survive lethal doses of IONIZING RADIATION. Tolerance depends on the species, cell type, and physical and chemical variables, including RADIATION-PROTECTIVE AGENTS and RADIATION-SENSITIZING AGENTS. Radiation Sensitivity,Radiosensitivity,Sensitivity, Radiation,Tolerance, Radiation,Radiation Sensitivities,Radiation Tolerances,Radiosensitivities,Sensitivities, Radiation,Tolerances, Radiation
D002874 Chromosome Mapping Any method used for determining the location of and relative distances between genes on a chromosome. Gene Mapping,Linkage Mapping,Genome Mapping,Chromosome Mappings,Gene Mappings,Genome Mappings,Linkage Mappings,Mapping, Chromosome,Mapping, Gene,Mapping, Genome,Mapping, Linkage,Mappings, Chromosome,Mappings, Gene,Mappings, Genome,Mappings, Linkage
D003922 Diabetes Mellitus, Type 1 A subtype of DIABETES MELLITUS that is characterized by INSULIN deficiency. It is manifested by the sudden onset of severe HYPERGLYCEMIA, rapid progression to DIABETIC KETOACIDOSIS, and DEATH unless treated with insulin. The disease may occur at any age, but is most common in childhood or adolescence. Diabetes Mellitus, Brittle,Diabetes Mellitus, Insulin-Dependent,Diabetes Mellitus, Juvenile-Onset,Diabetes Mellitus, Ketosis-Prone,Diabetes Mellitus, Sudden-Onset,Diabetes, Autoimmune,IDDM,Autoimmune Diabetes,Diabetes Mellitus, Insulin-Dependent, 1,Diabetes Mellitus, Type I,Insulin-Dependent Diabetes Mellitus 1,Juvenile-Onset Diabetes,Type 1 Diabetes,Type 1 Diabetes Mellitus,Brittle Diabetes Mellitus,Diabetes Mellitus, Insulin Dependent,Diabetes Mellitus, Juvenile Onset,Diabetes Mellitus, Ketosis Prone,Diabetes Mellitus, Sudden Onset,Diabetes, Juvenile-Onset,Diabetes, Type 1,Insulin Dependent Diabetes Mellitus 1,Insulin-Dependent Diabetes Mellitus,Juvenile Onset Diabetes,Juvenile-Onset Diabetes Mellitus,Ketosis-Prone Diabetes Mellitus,Sudden-Onset Diabetes Mellitus
D005720 Gamma Rays Penetrating, high-energy electromagnetic radiation emitted from atomic nuclei during NUCLEAR DECAY. The range of wavelengths of emitted radiation is between 0.1 - 100 pm which overlaps the shorter, more energetic hard X-RAYS wavelengths. The distinction between gamma rays and X-rays is based on their radiation source. Gamma Wave,Gamma Radiation,Nuclear X-Rays,Radiation, Gamma,X-Rays, Nuclear,Gamma Radiations,Gamma Ray,Gamma Waves,Nuclear X Rays,Nuclear X-Ray,Ray, Gamma,Wave, Gamma,Waves, Gamma,X Rays, Nuclear,X-Ray, Nuclear
D000069594 Abatacept A fusion protein immunoconjugate of the extracellular domain of CTLA4 and the Fc domain of human IgG1. It functions as a T-cell co-stimulation blocker that inhibits TNF-ALPHA and prevents the activation of T-LYMPHOCYTES. It is used in the treatment of RHEUMATOID ARTHRITIS. BMS 188667,BMS-188667,BMS-224818,BMS224818,Belatacept,CTLA-4-Ig,CTLA4-Fc,CTLA4-Ig,CTLA4-Ig Immunoconjugate,Cytotoxic T Lymphocyte-Associated Antigen 4-Immunoglobulin,LEA29Y,Nulojix,Orencia,BMS 224818,BMS188667,CTLA4 Ig Immunoconjugate,Cytotoxic T Lymphocyte Associated Antigen 4 Immunoglobulin,Immunoconjugate, CTLA4-Ig
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000943 Antigens, Differentiation Antigens expressed primarily on the membranes of living cells during sequential stages of maturation and differentiation. As immunologic markers they have high organ and tissue specificity and are useful as probes in studies of normal cell development as well as neoplastic transformation. Differentiation Antigen,Differentiation Antigens,Differentiation Antigens, Hairy Cell Leukemia,Differentiation Marker,Differentiation Markers,Leu Antigen,Leu Antigens,Marker Antigen,Marker Antigens,Markers, Differentiation,Antigen, Differentiation,Antigen, Leu,Antigen, Marker,Antigens, Leu,Antigens, Marker,Marker, Differentiation
D013601 T-Lymphocytes Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T Cell,T Lymphocyte,T-Cells,Thymus-Dependent Lymphocytes,Cell, T,Cells, T,Lymphocyte, T,Lymphocyte, Thymus-Dependent,Lymphocytes, T,Lymphocytes, Thymus-Dependent,T Cells,T Lymphocytes,T-Cell,T-Lymphocyte,Thymus Dependent Lymphocytes,Thymus-Dependent Lymphocyte
D013950 Thymus Gland A single, unpaired primary lymphoid organ situated in the MEDIASTINUM, extending superiorly into the neck to the lower edge of the THYROID GLAND and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat. Thymus,Gland, Thymus,Glands, Thymus,Thymus Glands
D015551 Autoimmunity Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by AUTOIMMUNE DISEASES. Autoimmune Response,Autoimmune Responses,Autoimmunities

Related Publications

M L Bergman, and C M Cilio, and C Penha-Gonçalves, and S E Lamhamedi-Cherradi, and A Löfgren, and F Colucci, and K Lejon, and H J Garchon, and D Holmberg
December 1997, Clinical and experimental immunology,
M L Bergman, and C M Cilio, and C Penha-Gonçalves, and S E Lamhamedi-Cherradi, and A Löfgren, and F Colucci, and K Lejon, and H J Garchon, and D Holmberg
December 2021, Diabetes,
M L Bergman, and C M Cilio, and C Penha-Gonçalves, and S E Lamhamedi-Cherradi, and A Löfgren, and F Colucci, and K Lejon, and H J Garchon, and D Holmberg
December 1998, Journal of autoimmunity,
M L Bergman, and C M Cilio, and C Penha-Gonçalves, and S E Lamhamedi-Cherradi, and A Löfgren, and F Colucci, and K Lejon, and H J Garchon, and D Holmberg
November 2007, The Journal of biological chemistry,
M L Bergman, and C M Cilio, and C Penha-Gonçalves, and S E Lamhamedi-Cherradi, and A Löfgren, and F Colucci, and K Lejon, and H J Garchon, and D Holmberg
May 1999, Clinical and experimental immunology,
M L Bergman, and C M Cilio, and C Penha-Gonçalves, and S E Lamhamedi-Cherradi, and A Löfgren, and F Colucci, and K Lejon, and H J Garchon, and D Holmberg
January 1998, Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association,
M L Bergman, and C M Cilio, and C Penha-Gonçalves, and S E Lamhamedi-Cherradi, and A Löfgren, and F Colucci, and K Lejon, and H J Garchon, and D Holmberg
January 1992, Comptes rendus de l'Academie des sciences. Serie III, Sciences de la vie,
M L Bergman, and C M Cilio, and C Penha-Gonçalves, and S E Lamhamedi-Cherradi, and A Löfgren, and F Colucci, and K Lejon, and H J Garchon, and D Holmberg
May 1992, Immunology,
M L Bergman, and C M Cilio, and C Penha-Gonçalves, and S E Lamhamedi-Cherradi, and A Löfgren, and F Colucci, and K Lejon, and H J Garchon, and D Holmberg
January 2013, PloS one,
M L Bergman, and C M Cilio, and C Penha-Gonçalves, and S E Lamhamedi-Cherradi, and A Löfgren, and F Colucci, and K Lejon, and H J Garchon, and D Holmberg
March 1989, Clinical and experimental immunology,
Copied contents to your clipboard!