GAD-reactive T cells were mainly detected in autoimmune-related type 1 diabetic patients with HLA DR9.
Type 1 diabetes mellitus (T1DM) is considered to be a T cell-mediated disease, and many reports suggest that some HLA types, especially HLA DR4 and DR9, convey susceptibility to T1DM in Japanese. We investigated the association between T cell reactivity against GAD and HLA types in "islet-associated autoantibody-positive" T1DM in Japanese. Blood samples were obtained from 36 "autoantibody-positive" type 1 diabetic patients with HLA DR4 or DR9 and 23 type 2 diabetic patients with HLA DR4 or DR9 as controls. They were divided into three groups, DR4/9, DR4/X, and DR9/X groups. In each HLA type group, GAD-reactive IFN-gamma-producing CD4(+) cells were assessed by means of intracellular cytokine staining for flow cytometry. Type 1 diabetic patients with HLA DR9/X had significantly higher numbers of GAD-reactive IFN-gamma-producing CD4(+) cells as compared to type 1 diabetic patients with DR4/X or DR4/9 (P < 0.05) and all type 2 diabetic patients. There was no significant difference in the number of GAD-reactive IFN-gamma-producing CD4(+) cells between type 1 diabetic and type 2 diabetic patients belonging to the DR4/X and DR4/9 groups. There was an association between T cell reactivity against GAD and HLA DR9 in Japanese type 1 diabetes.
Itoh
Arata
A
Department of Internal Medicine, Keio Univ. School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Shimada
Akira
A
Kodama
Keiichi
K
Morimoto
Jiro
J
Suzuki
Ryuji
R
Oikawa
Yoichi
Y
Irie
Junichiro
J
Nakagawa
Yoshinori
Y
Shigihara
Toshikatsu
T
Kanazawa
Yasuhiko
Y
Okubo
Yoshiaki
Y
Motohashi
Yoshiko
Y
Maruyama
Taro
T
Saruta
Takao
T
D000328:Adult; D000368:Aged; D044466:Asian People; D001323:Autoantibodies / Q000097:blood; D001324:Autoantigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D003924:Diabetes Mellitus, Type 2; D005260:Female; D005434:Flow Cytometry; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006684:HLA-DR Antigens / Q000235:genetics*; D015804:HLA-DR4 Antigen / Q000235:genetics; D006650:Histocompatibility Testing; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000276:immunology; D008875:Middle Aged; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000276:immunology; D011869:Radioligand Assay; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D013601:T-Lymphocytes / Q000201:enzymology*
D001323:Autoantibodies; D001324:Autoantigens; D006684:HLA-DR Antigens; D015804:HLA-DR4 Antigen; D008565:Membrane Proteins; D007371:Interferon-gamma; C516862:PTPRN protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D005968:Glutamate Decarboxylase