Effect of interferon-gamma and glucose on major histocompatibility complex class I and class II expression by pancreatic beta- and non-beta-cells.
Surface major histocompatibility complex (MHC) class I and class II expression by pancreatic islet cells is considered a local initiator or regulator of immune processes that can lead to diabetes. Locally released cytokines, in particular interferon-gamma, are known to stimulate MHC antigen expression by islet cells. The present study quantifies MHC expression in cultured pancreatic beta- and non-beta-cells from both rat and human organs. Interferon-gamma increased MHC class I expression in endocrine beta- and non-beta-cells as well as in pancreatic ductal cells. The cytokine induced a 6-fold increase in the MHC class I messenger ribonucleic acid levels in pancreatic beta-cells; this effect was 2-fold amplified in the presence of elevated glucose levels (20 mmol/L instead of 6 mmol/L). No MHC class II expression was observed in endocrine beta- or non-beta-cells; human, but not rat, ductal cells exhibited MHC class II expression that increased in the presence of interferon-gamma. These data indicate that the increase in beta-cell MHC class I expression described in the pancreata of diabetic patients may result from stimulated transcription after exposure to locally released interferon-gamma and/or to a hyperglycemic state. The association of human islets with ductal cells in which MHC class II expression is stimulated by interferon-gamma makes these cells potential participants in the autoimmune process in diabetes.
Pavlovic
D
D
Diabetes Research Center, Vrije University Brussel, Belgium.
van de Winkel
M
M
van der Auwera
B
B
Chen
M C
MC
Schuit
F
F
Bouwens
L
L
Pipeleers
D
D
D000293:Adolescent; D000328:Adult; D000818:Animals; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D005947:Glucose / Q000494:pharmacology*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007633:Keratins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D001613:beta 2-Microglobulin / Q000378:metabolism
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D001613:beta 2-Microglobulin; D007633:Keratins; D007371:Interferon-gamma; D005947:Glucose