T cell reactivity to human insulinoma cell line (CM) antigens in patients with type 1 diabetes

Autoimmune (type 1) diabetes mellitus results from a progressive destructio n of insulin secreting beta cells operated by T lymphocytes in pancreatic i slets, Circulating autoreactive T cells to specific beta cell antigens are detected in patients with type 1 diabetes. To date, several beta cell autoa ntigens have been identified in this disease (GAD, IA-2, 38 kD secretory pr otein, insulin, ICA69 etc.), however, it is possible that also other uniden tified self molecules contribute to trigger beta cell autoimmunity. In this study we used the human insulinoma cell line CM as source of beta c ell antigens to detect reactive T lymphocytes in patients with type 1 diabe tes mellitus, This cell line has been previously shown to express a number of recognized beta cell antigens, Since the expression of several beta cell antigens is affected by glucose stimulation we tested two preparations of CM cells cultured under different conditions containing low (0.8 mM) and hi gh glucose concentration (11 mM). T cell proliferation was measured using c ells from 32 patients with type 1 diabetes (19 of recent onset and 13 at 3 to 22 months from diagnosis) and 27 age-matched control subjects. A significant increase in T cell proliferation to CRI cells grown in high g lucose conditions (11 mM) (p < 0.05) was found in type 1 diabetic patients compared to controls. No significant differences were observed when using C M cells cultured at the low glucose concentration. Furthermore, the respons e to both extracts of CM cells was independent of disease duration (p = 0.6 for both CM cells cultured at 0.8 and 11 mM glucose). These data indicate that T cell reactivity to homogenates of CIM cells is d etectable in patients with type 1 diabetes and suggest that this human insu linoma cell line is an interesting potential source of beta cell material f or immunological studies of autoimmune diabetes.