BETA CELLS IN TYPE 1 DIABETES: VICTIMS OR ACTIVATORS OF T CELL RESPONSE?

T he hallmark of type 1 diabetes is the spe-cific destruction of pancreatic beta cells.This common disease affects 0.5 % of thepopulation in developed countries and 5 to 10 % of people originally diagnosed as type 2 diabetics have a less severe form of the disease called Latent Autoimmune Diabetes of Adults (LADA). A large body of evidences both from experi-mental and clinical origins has suggested that this specific beta cell loss results from an autoimmune-mediated phenomenon [1, 2]. This chronic process may take several years and is associated with insulitis, when most of the islets are invaded by mononuclear cells, including dendritic cells and T lymphocytes. However, despite a correlation between peripheral markers such as anti-GAD or anti-IA2 antibodies and beta cell destruction, in vivo analysis of insulitis in type 1 diabetics of recent onset has revealed a fraction of patients without autoimmune patterns [3]. In addi-tion, several important issues remain unsolved nearly 40 years after the first discovery of islet cell infiltra-tion figures in the pancreas of a type 1 diabetic pa-tients by Willy Gepts [4]. Among these unsolved ques-tions, stand the characterization of an hypothetical triggering factor of the autoimmune reaction, the pu-tative roles played by environmental or genetic factors in regulating its progression and the final effector mechanisms leading to beta cell destruction. Face with these difficulties, animals models, in particular the non-obese diabetic (NOD) mouse and transgenic de-rivatives of it, have provided extensive knowledge on the very early phases of the process and on the com-plex interactions between genes and T cell function [5]. However, transfers of animal data to the human situation remain to be evaluated due to the important heterogeneity of the genetic background. Physiologi-cal, metabolic and immune-mediated destructions of beta cells may be crucial key events that may initiate or control the progression to disease