Numerous investigation have demonstrated that T cells are involved in destruction of beta cells in the NOD mouse, a widely studied model of type I diabetes. In this report we describe a series of islet-specific T cell lines established from islet-infiltrating lymphocytes obtained from individual pre-diabetic NOD mice as well as a large panel of clones derived from these lines. Proliferation assays indicated that these nominally islet-specific lines responded vigorously to porcine insulin. Furthermore, of 40 islet-specific clones derived from lines established from 12-week-old mice, 22 (55%) responded to insulin. A similar analysis of islet-specific clones established from 7-week-old mice indicated that 2 of 14 (14%) were insulin specific. These findings demonstrate that insulin-specific T cells can comprise a major portion of the spontaneously arising T cell response to islets in NOD mice.

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There is compelling evidence from animal models that type I diabetes is a consequence of T cell-mediated destruction of islet beta-cells. The recent isolation of islet-specific T cell clones from nonobese diabetic mice provides a means of identification of the Ag on islet cells that are responsible for stimulation of autoreactive T cells. We describe an APC line constructed by fusion of spleen B cells obtained from nonobese diabetic mice to a B lymphoma that was transfected with the H and L chains of an IgM specific to the hapten TNP. Using this hybrid APC we have observed a dramatic increase in the efficiency of presentation of TNP-conjugated islet cell protein preparations compared to that seen with conventional APC. Our results illustrate the potential use of this APC line for isolation and characterization of islet Ag relevant to the T cell response.