D. Pavlovic et al., EFFECT OF INTERFERON-GAMMA AND GLUCOSE ON MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I AND CLASS-II EXPRESSION BY PANCREATIC BETA-CELLS AND NON-BETA-CELLS, The Journal of clinical endocrinology and metabolism, 82(7), 1997, pp. 2329-2336
Surface major histocompatibility complex (MHC) class I and class II ex
pression by pancreatic islet cells is considered a local initiator or
regulator of immune processes that can lead to diabetes. Locally relea
sed cytokines, in particular interferon-gamma, are known to stimulate
MHC antigen expression by islet cells. The present study quantifies MH
C expression in cultured pancreatic beta- and non-beta-cells from both
rat and human organs. Interferon-gamma increased MHC class I expressi
on in endocrine beta- and non-beta-cells as well as in pancreatic duct
al cells. The cytokine induced a 6-fold increase in the MHC class I me
ssenger ribonucleic acid levels in pancreatic beta-cells; this effect
was 2-fold amplified in the presence of elevated glucose levels (20 mm
ol/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 ex
hibited MHC class II expression that increased in the presence of inte
rferon-gamma. These data indicate that the increase in beta-cell MHC c
lass I expression described in the pancreata of diabetic patients may
result from stimulated transcription after exposure to locally release
d interferon-gamma and/or to a hyperglycemic state. The association of
human islets with ductal cells in which MHC class II expression is st
imulated by interferon-gamma makes these cells potential participants
in the autoimmune process in diabetes.