T cells reacting with pancreatic islet beta cell
proteins play a pivotal role in the pathogenesis of
type 1 diabetes in experimental animal models and man, although the islet cell
autoantigens against which these T cells are directed remain to be characterized. We have previously shown the presence of disease-related
antigens residing in the transplantable RIN
insulinoma membranes which are recognized by T cells from diabetic NOD mice. We now report on the establishment of CD4+, T cell lines reacting with
insulinoma membranes from six newly diagnosed type 1 diabetic patients. Detailed examination of T cell lines from two patients revealed that both the lines continued to react with normal islet cell
proteins and, interestingly, were also stimulated by
antigens present in brain microsomes. The two T cell lines showed reactivity with different molecular weight
proteins of the
insulinoma membranes and both the lines were histocompatibility-linked
antigen (
HLA)-DR restricted. Although the
insulinoma membrane preparation is known to contain
glutamic acid decarboxylase (GAD), none of the six T cell lines proliferates in response to purified GAD. These T cell lines will be valuable in characterizing novel islet beta cell
antigens which are likely to be implicated in
type 1 diabetes.