Mononuclear cell infiltration and its relation to the expression of major histocompatibility complex antigens and adhesion molecules in pancreas biopsy specimens from newly diagnosed insulin-dependent diabetes mellitus patients.
We examined pancreas biopsy specimens from 18 newly diagnosed insulin-dependent diabetes mellitus (IDDM) patients to elucidate the mechanism underlying beta cell destruction. Pancreas islets were seen in all patients and insulitis in eight patients. Infiltrating mononuclear cells consisted of CD4+T, CD8+T, B lymphocytes, and macrophages. Among them, CD8+T lymphocytes were predominant and macrophages followed. The expression of MHC class I antigens was increased in islet and endothelial cells in nine patients. MHC class II expression was increased in endothelial cells of the same patients. The expression of intercellular adhesion molecule-1 was increased in endothelial cells in two of the nine patients with MHC hyperexpression; in one of them, lymphocyte function-associated antigen-3 expression was also increased. Out of the eight patients with insulitis, seven showed MHC class I hyper-expression, whereas 2 of the 10 patients without insulitis showed the phenomenon (P < 0.05). The relation between insulitis and the hyperexpression of adhesion molecules was not evident. In conclusion, we revealed the close relation between CD8+T lymphocyte-predominant insulitis and MHC class I hyperexpression in islet cells. This suggests that infiltrating CD8+T lymphocytes recognize islet autoantigens in association with increased MHC class I molecules and act as major effector cells in autoimmune response against islet cells in IDDM pancreases. The role of adhesion molecules in the pathogenesis of IDDM still remains to be elucidated.
Itoh
N
N
Second Department of Internal Medicine, Osaka University Medical School, Japan.
Hanafusa
T
T
Miyazaki
A
A
Miyagawa
J
J
Yamagata
K
K
Yamamoto
K
K
Waguri
M
M
Imagawa
A
A
Tamura
S
S
Inada
M
M
D000293:Adolescent; D000328:Adult; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology; D001706:Biopsy; D017252:CD3 Complex / Q000302:isolation & purification; D015704:CD4 Antigens / Q000302:isolation & purification; D016827:CD8 Antigens / Q000302:isolation & purification; D015815:Cell Adhesion Molecules / Q000032:analysis; D002465:Cell Movement; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis / Q000276:immunology*; D005260:Female; D005455:Fluorescent Antibody Technique; D005934:Glucagon / Q000302:isolation & purification; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000276:immunology; D010195:Pancreatitis / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D015815:Cell Adhesion Molecules; D005934:Glucagon