FAILURE OF A PROTECTIVE MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II MOLECULE TO DELETE AUTOREACTIVE T-CELLS IN AUTOIMMUNE DIABETES

The association of major histocompatibility complex genes with autoimm une diseases is firmly established, but the mechanisms by which these genes confer resistance or susceptibility remain controversial. The co ntroversy extends to the nonobese diabetic (NOD) mouse that develops d isease similar to human insulin-dependent diabetes mellitus. The trans genic incorporation of certain class II major histocompatibility compl ex genes protects NOD mice from diabetes, and clonal deletion or funct ional silencing of autoreactive T cells has been proposed as the mecha nism by which these molecules provide protection. We show that neither thymic deletion nor anergy of autoreactive T cells occurs in NOD mice transgenic for I-A(k). Autoreactive T cells are present, functional, and can transfer diabetes to appropriate NOD-recipient mice.