Introduction

The expression of MHC products by pancreatic islet cells has been extensively studied because these cells are the targets of the destructive autoimmune response that leads to insulin-dependent diabetes mellitus (IDDM) and also because they constitute a set of distinct cell populations ideal for the study of peripheral tolerance by gene targeting in transgenic (tg) mice. Many of the studies described in this chapter were first prompted by concepts previously proposed in the aberrant class II expression hypothesis of endocrine autoimmunity (Bottazzo et al., 1983).

The aberrant class II expression hypothesis of endocrine autoimmunity

Aberrant (actually ectopic) HLA class II expression, i.e. the expression of HLA class II by cells of lineages that are normally class II negative, was first detected in the thyroid follicular cells of glands resected from patients suffering from autoimmune thyrotoxicosis, or Graves' disease (Hanafusa et al., 1983). This finding, together with the demonstration that thyroid follicular cells can be induced to express HLA class II antigens in vitro (Pujol-Borrell et al., 1983), led to the formulation of the aberrant class II expression hypothesis. This is based on the assumption that the lack of active immune response to endocrine cells and other scarce and differentiated cells present in peripheral tissues is the result of their low expression of HLA proteins, which makes them ‘invisible’ to T cells (immunological silence).