scholarly journals A crucial role of CD4 T cells as a functional source of CD154 in the initiation of insulin-dependent diabetes mellitus in the non-obese diabetic mouse

2003 ◽  
Vol 15 (3) ◽  
pp. 351-357 ◽  
Author(s):  
K. Eshima
Keyword(s):  
Diabetes Mellitus ◽  
T Cells ◽  
Crucial Role ◽  
Cd4 T Cells ◽  
Insulin Dependent Diabetes Mellitus ◽  
Diabetic Mouse ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Insulin Dependent

scholarly journals Higher autoantibody levels and recognition of a linear NH2-terminal epitope in the autoantigen GAD65, distinguish stiff-man syndrome from insulin-dependent diabetes mellitus.

1994 ◽  
Vol 180 (2) ◽  
pp. 595-606 ◽  
Author(s):  
J Kim ◽  
M Namchuk ◽  
T Bugawan ◽  
Q Fu ◽  
M Jaffe ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
T Cells ◽  
Cd4 T Cells ◽  
Insulin Dependent Diabetes Mellitus ◽  
Insulin Dependent Diabetes ◽  
Cytotoxic T Cell ◽  
Dependent Diabetes Mellitus ◽  
Western Blots ◽  
Insulin Dependent ◽  
Stiff Man Syndrome

The smaller form of the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD65) is a major autoantigen in two human diseases that affect its principal sites of expression. Thus, destruction of pancreatic beta cells, which results in insulin-dependent diabetes mellitus (IDDM), and impairment of GABA-ergic synaptic transmission in Stiff-Man syndrome (SMS) are both characterized by circulating autoantibodies to GAD65. Anti-GAD65 autoantibodies in IDDM are predominantly directed to conformational epitopes. Here we report the characterization of humoral autoimmune responses to GAD65 in 35 SMS patients, of whom 13 (37%) also had IDDM. All SMS patients immunoprecipitated native GAD65 and the main titers were orders of magnitude higher than in IDDM patients. Furthermore, in contrast to the situation in IDDM, autoantibodies in 35 of 35 (100%) of SMS patients recognized denatured GAD65 on Western blots. Two major patterns of epitope specificity were identified on Western blots. The first pattern, detected in 25 of 35 SMS patients (71%), of whom 11 had IDDM (44%), was predominantly reactive with a linear NH2-terminal epitope residing in the first eight amino acids of GAD65. Nine of nine individuals who were HLA-haplotyped in this group carried an IDDM susceptibility haplotype and HLA-DR3, DQw2 was particularly abundant. The second pattern, detected in 10 of 35 patients (29%) of whom two had IDDM (20%), included reactivity with the NH2-terminal epitope plus strong reactivity with one or more additional epitope(s) residing COOH-terminal to amino acid 101. The second epitope pattern may represent epitope spreading in the GAD65 molecule, but may also include some cases of epitope recognition associated with IDDM resistant HLA-haplotypes. The principal NH2-terminal linear epitope in GAD65 distinguishes the reactivity of SMS and IDDM autoantibodies and may be a determinant of pathogenicity for GABA-ergic neurons. The greater magnitude and distinct specificity of the humoral response to GAD65 in SMS may reflect a biased involvement of the T helper cell type 2 (Th2) subset of CD4+ T cells and antibody responses, whereas IDDM is likely mediated by the Th1 subset of CD4+ T cells and cytotoxic T cell responses.

The role of CD8+ T cells in the initiation of insulin-dependent diabetes mellitus

1996 ◽  
Vol 26 (8) ◽  
pp. 1762-1769 ◽  
Author(s):  
Bo Wang ◽  
Antonio Gonzalez ◽  
Christophe Benoist ◽  
Diane Mathis
Keyword(s):  
Diabetes Mellitus ◽  
T Cells ◽  
Cd8 T Cells ◽  
Insulin Dependent Diabetes Mellitus ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Insulin Dependent

The development of insulin-dependent diabetes mellitus in non-obese diabetic mice: the role of CD4+ and CD8+ T cells

1991 ◽  
Vol 19 (1) ◽  
pp. 187-191 ◽  
Author(s):  
Anne-Marie Varey ◽  
Patricia Hutchings ◽  
Lorraine O'Reilly ◽  
Tracey Hussell ◽  
Herman Waldmann ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
T Cells ◽  
Cd8 T Cells ◽  
Insulin Dependent Diabetes Mellitus ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Diabetic Mice ◽  
Insulin Dependent
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