Chairman’s Summing up

Abstract

I think for our understanding of autoimmunity we are going to have to know what the genes are that are involved in susceptibility to the development of these diseases. In relation to type I diabetes, 3 species develop the disease, the BB rat, the NOD mouse and man. Its clear that there are at least two genes conferring susceptibility; one is a gene that destroys or leads to the absence of all RT6 positive T lymphocytes and the other is an MHC gene which has been very well localized to the class II region where there are recombinants on both sides of the class II region and the disease is carried within the class II region. It is not known whether its an IA or IE like gene. In addition, in the BB rat there is a severe T cell lymphopenia gene that is inherited as a simple autosome recessive gene creating an immunodeficient rat which has in the order of a 100 to a 1000 times greater incidence of diabetes compared to a rat which only has the MHC susceptibility gene. Also I might just mention that BB rats have no CD8 T lymphocytes. They are apparently killing their beta cells without any of the classic CD8+ T cells. Hence, it has been virtually impossible to breed a strain that consistently develops type I diabetes in the absence of the T cell lymphopinia gene.