Fas/Fas ligand interactions play an essential role in the initiation of murine autoimmune diabetes. 2002

Maki Nakayama, and Masao Nagata, and Hisafumi Yasuda, and Kenji Arisawa, and Reiko Kotani, and Katsumi Yamada, and Shahead Ali Chowdhury, and Sagarika Chakrabarty, and Zhen Zi Jin, and Hideo Yagita, and Koichi Yokono, and Masato Kasuga
Department of Diabetes, Digestive and Kidney Diseases, Kobe University Graduate School of Medicine, Kobe, Japan.

Apoptosis via Fas/Fas ligand (FasL) interactions has been proposed to be a major T-cell-mediated effector mechanism in autoimmune diabetes. To elucidate the role of Fas/FasL interactions in NOD diabetes, the effects of neutralizing anti-FasL antibody on autoimmune responses were evaluated. Islet-specific CD8(+) and CD4(+) T-cells expressed FasL upon activation and mediated FasL-dependent cytotoxicity against Fas-expressing target cells in vitro, although their cytotoxicity against islet cells was not blocked by anti-FasL antibody. Moreover, administration of anti-FasL antibody failed to inhibit diabetes in vivo in the CD8(+) T-cell adoptive transfer model. On the other hand, blockade of Fas/FasL interactions significantly inhibited CD4(+) T-cell-dependent diabetes in adoptive transfer models. These results suggest a substantial contribution of Fas/FasL interactions to CD4(+), but not CD8(+), T-cell-mediated destruction of pancreatic beta-cells. When anti-FasL antibody was administered to NOD mice between 5 and 15 weeks of age, the onset of diabetes was slightly delayed but the incidence was not decreased. However, administration of anti-FasL antibody at 2-4 weeks of age completely prevented insulitis and diabetes. These results suggest that Fas/FasL interactions contribute to CD4(+) T-cell-mediated beta-cell destruction and play an essential role in the initiation of autoimmune NOD diabetes.

UI MeSH Term Description Entries
D007515 Islets of Langerhans Irregular microscopic structures consisting of cords of endocrine cells that are scattered throughout the PANCREAS among the exocrine acini. Each islet is surrounded by connective tissue fibers and penetrated by a network of capillaries. There are four major cell types. The most abundant beta cells (50-80%) secrete INSULIN. Alpha cells (5-20%) secrete GLUCAGON. PP cells (10-35%) secrete PANCREATIC POLYPEPTIDE. Delta cells (~5%) secrete SOMATOSTATIN. Islands of Langerhans,Islet Cells,Nesidioblasts,Pancreas, Endocrine,Pancreatic Islets,Cell, Islet,Cells, Islet,Endocrine Pancreas,Islet Cell,Islet, Pancreatic,Islets, Pancreatic,Langerhans Islands,Langerhans Islets,Nesidioblast,Pancreatic Islet
D008297 Male Males
D008562 Membrane Glycoproteins Glycoproteins found on the membrane or surface of cells. Cell Surface Glycoproteins,Surface Glycoproteins,Cell Surface Glycoprotein,Membrane Glycoprotein,Surface Glycoprotein,Glycoprotein, Cell Surface,Glycoprotein, Membrane,Glycoprotein, Surface,Glycoproteins, Cell Surface,Glycoproteins, Membrane,Glycoproteins, Surface,Surface Glycoprotein, Cell,Surface Glycoproteins, Cell
D003601 Cytotoxicity Tests, Immunologic The demonstration of the cytotoxic effect on a target cell of a lymphocyte, a mediator released by a sensitized lymphocyte, an antibody, or complement. AHG-CDC Tests,Anti-Human Globulin Complement-Dependent Cytotoxicity Tests,Microcytotoxicity Tests,Anti Human Globulin Complement Dependent Cytotoxicity Tests,Anti-Human Globulin Complement-Dependent Cytotoxicity Test,Antiglobulin-Augmented Lymphocytotoxicity Test,Antiglobulin-Augmented Lymphocytotoxicity Tests,Cytotoxicity Test, Immunologic,Cytotoxicity Tests, Anti-Human Globulin Complement-Dependent,Cytotoxicity Tests, Immunological,Immunologic Cytotoxicity Test,Immunologic Cytotoxicity Tests,Lymphocytotoxicity Test, Antiglobulin-Augmented,Lymphocytotoxicity Tests, Antiglobulin-Augmented,Microcytotoxicity Test,AHG CDC Tests,AHG-CDC Test,Anti Human Globulin Complement Dependent Cytotoxicity Test,Antiglobulin Augmented Lymphocytotoxicity Test,Antiglobulin Augmented Lymphocytotoxicity Tests,Cytotoxicity Test, Immunological,Cytotoxicity Tests, Anti Human Globulin Complement Dependent,Immunological Cytotoxicity Test,Immunological Cytotoxicity Tests,Lymphocytotoxicity Test, Antiglobulin Augmented,Lymphocytotoxicity Tests, Antiglobulin Augmented
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
D005260 Female Females
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
D000906 Antibodies Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).
D015496 CD4-Positive T-Lymphocytes A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes. T4 Cells,T4 Lymphocytes,CD4-Positive Lymphocytes,CD4 Positive T Lymphocytes,CD4-Positive Lymphocyte,CD4-Positive T-Lymphocyte,Lymphocyte, CD4-Positive,Lymphocytes, CD4-Positive,T-Lymphocyte, CD4-Positive,T-Lymphocytes, CD4-Positive,T4 Cell,T4 Lymphocyte
D016688 Mice, Inbred NOD A strain of non-obese diabetic mice developed in Japan that has been widely studied as a model for T-cell-dependent autoimmune insulin-dependent diabetes mellitus in which insulitis is a major histopathologic feature, and in which genetic susceptibility is strongly MHC-linked. Non-Obese Diabetic Mice,Mice, NOD,Mouse, Inbred NOD,Mouse, NOD,Non-Obese Diabetic Mouse,Nonobese Diabetic Mice,Nonobese Diabetic Mouse,Diabetic Mice, Non-Obese,Diabetic Mice, Nonobese,Diabetic Mouse, Non-Obese,Diabetic Mouse, Nonobese,Inbred NOD Mice,Inbred NOD Mouse,Mice, Non-Obese Diabetic,Mice, Nonobese Diabetic,Mouse, Non-Obese Diabetic,Mouse, Nonobese Diabetic,NOD Mice,NOD Mice, Inbred,NOD Mouse,NOD Mouse, Inbred,Non Obese Diabetic Mice,Non Obese Diabetic Mouse

Related Publications

Maki Nakayama, and Masao Nagata, and Hisafumi Yasuda, and Kenji Arisawa, and Reiko Kotani, and Katsumi Yamada, and Shahead Ali Chowdhury, and Sagarika Chakrabarty, and Zhen Zi Jin, and Hideo Yagita, and Koichi Yokono, and Masato Kasuga
September 1998, Diabetes/metabolism reviews,
Maki Nakayama, and Masao Nagata, and Hisafumi Yasuda, and Kenji Arisawa, and Reiko Kotani, and Katsumi Yamada, and Shahead Ali Chowdhury, and Sagarika Chakrabarty, and Zhen Zi Jin, and Hideo Yagita, and Koichi Yokono, and Masato Kasuga
April 1997, Cell,
Maki Nakayama, and Masao Nagata, and Hisafumi Yasuda, and Kenji Arisawa, and Reiko Kotani, and Katsumi Yamada, and Shahead Ali Chowdhury, and Sagarika Chakrabarty, and Zhen Zi Jin, and Hideo Yagita, and Koichi Yokono, and Masato Kasuga
November 2004, World journal of gastroenterology,
Maki Nakayama, and Masao Nagata, and Hisafumi Yasuda, and Kenji Arisawa, and Reiko Kotani, and Katsumi Yamada, and Shahead Ali Chowdhury, and Sagarika Chakrabarty, and Zhen Zi Jin, and Hideo Yagita, and Koichi Yokono, and Masato Kasuga
June 2006, Nature clinical practice. Endocrinology & metabolism,
Maki Nakayama, and Masao Nagata, and Hisafumi Yasuda, and Kenji Arisawa, and Reiko Kotani, and Katsumi Yamada, and Shahead Ali Chowdhury, and Sagarika Chakrabarty, and Zhen Zi Jin, and Hideo Yagita, and Koichi Yokono, and Masato Kasuga
November 2003, Annals of the New York Academy of Sciences,
Maki Nakayama, and Masao Nagata, and Hisafumi Yasuda, and Kenji Arisawa, and Reiko Kotani, and Katsumi Yamada, and Shahead Ali Chowdhury, and Sagarika Chakrabarty, and Zhen Zi Jin, and Hideo Yagita, and Koichi Yokono, and Masato Kasuga
October 1996, Gastroenterology,
Maki Nakayama, and Masao Nagata, and Hisafumi Yasuda, and Kenji Arisawa, and Reiko Kotani, and Katsumi Yamada, and Shahead Ali Chowdhury, and Sagarika Chakrabarty, and Zhen Zi Jin, and Hideo Yagita, and Koichi Yokono, and Masato Kasuga
April 2002, Annals of the New York Academy of Sciences,
Maki Nakayama, and Masao Nagata, and Hisafumi Yasuda, and Kenji Arisawa, and Reiko Kotani, and Katsumi Yamada, and Shahead Ali Chowdhury, and Sagarika Chakrabarty, and Zhen Zi Jin, and Hideo Yagita, and Koichi Yokono, and Masato Kasuga
July 2003, International immunopharmacology,
Maki Nakayama, and Masao Nagata, and Hisafumi Yasuda, and Kenji Arisawa, and Reiko Kotani, and Katsumi Yamada, and Shahead Ali Chowdhury, and Sagarika Chakrabarty, and Zhen Zi Jin, and Hideo Yagita, and Koichi Yokono, and Masato Kasuga
February 1999, European journal of immunology,
Maki Nakayama, and Masao Nagata, and Hisafumi Yasuda, and Kenji Arisawa, and Reiko Kotani, and Katsumi Yamada, and Shahead Ali Chowdhury, and Sagarika Chakrabarty, and Zhen Zi Jin, and Hideo Yagita, and Koichi Yokono, and Masato Kasuga
January 1999, Human gene therapy,
Copied contents to your clipboard!