Correlation between intracellular interferon-gamma (IFN-gamma) production by CD4+ and CD8+ lymphocytes and IFN-gamma gene polymorphism in patients with type 2 diabetes mellitus and latent autoimmune diabetes of adults (LADA).
IFN-gamma is considered to be involved in the pathogenesis of diabetes mellitus. In this study, the presence of T/A mutation at position -874 in IFN-gamma gene was assessed in patients with latent autoimmune diabetes of adults (LADA), in patients with type 2 diabetes and in healthy individuals. Subsequently, an attempt was made to correlate the presence of this mutation with the ability of CD4+ or CD8+ lymphocytes from these individuals to release IFN-gamma following mitogenic stimulation. There were no significant differences in the distribution of genotypes and haplotypes in the three study groups. However, the frequency of the low IFN-gamma production allele (IFN-gamma 874( *)A) was significantly higher in type 2 diabetics compared to controls. CD4+ and CD8+ cells obtained from type 2 diabetics released significantly lower amounts of IFN-gamma in the intracellular space, compared to those released by cells obtained from LADA patients and healthy volunteers. Furthermore, even CD4+ and CD8+ from type 2 diabetics bearing the TT genotype (high producers) released significantly lower amounts of IFN-gamma than LADA patients carrying the same genotype, probably due to the activity of molecules directly or indirectly inhibiting IFN-gamma production. The results of this study indicate that IFN-gamma may contribute to the development of type 2 diabetes, based on a combination of molecular and immunological observations.
Tsiavou
A
A
Onassis Cardiac Surgery Center, Molecular Immunopathology and Histocompatibility Laboratory, 356 Sygrou Avenue, Athens 17674, Greece. tsiavounat@yahoo.com
Hatziagelaki
E
E
Chaidaroglou
A
A
Koniavitou
K
K
Degiannis
D
D
Raptis
S A
SA
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D008213:Lymphocyte Activation; D008875:Middle Aged; D011110:Polymorphism, Genetic
D007371:Interferon-gamma