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Peripheral blood mononuclear cells of insulin-dependent diabetic patients respond to multiple islet cell proteins.

B M Brooks-Worrell, G A Starkebaum, C Greenbaum and J P Palmer
J Immunol December 15, 1996, 157 (12) 5668-5674;
B M Brooks-Worrell
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G A Starkebaum
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C Greenbaum
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J P Palmer
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Abstract

Insulin-dependent diabetes (IDDM) results from autoimmune destruction of pancreatic beta cells mediated predominantly by cellular effector mechanisms. To date, investigators have studied a limited number of islet cell proteins stimulatory to T cells. However, before development of clinical IDDM, the majority of the beta cells are impaired or destroyed. Thus, numerous proteins from lysed beta cells would be accessible to the immune system of the patient. Our goal was to investigate the PBMC reactivity of IDDM patients to the full spectrum of fractionated human pancreatic islet cell proteins to determine whether numerous islet cell proteins or a select few would be recognized. We observed that PBMCs from IDDM patients responded reproducibly (mean stimulation index, >2.0) to the proteins in all m.w. regions, whereas the mean stimulation index for controls from all m.w. regions was <2.0. Using three different islet protein preparations, PBMC responses of IDDM patients (n = 30) and controls (n = 39) to the islet cell proteins were significantly different. Dose responses were also demonstrated for the lymphocyte reactivity of the IDDM patients (n = 29) vs controls (n = 56) to the islet cell preparations. Proteins, presumably irrelevant to the IDDM disease process, from a human osteosarcoma cell line and normal human spleen cells did not stimulate PBMCs from IDDM patients or controls. Moreover, IDDM patients and controls responded similarly to mitogens and tetanus toxoid. These studies show that at the time of diagnosis of IDDM, PBMCs from IDDM patients are stimulated by a wide array of islet cell proteins.

  • Copyright © 1996 by American Association of Immunologists

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The Journal of Immunology
Vol. 157, Issue 12
15 Dec 1996
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Peripheral blood mononuclear cells of insulin-dependent diabetic patients respond to multiple islet cell proteins.
B M Brooks-Worrell, G A Starkebaum, C Greenbaum, J P Palmer
The Journal of Immunology December 15, 1996, 157 (12) 5668-5674;

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Peripheral blood mononuclear cells of insulin-dependent diabetic patients respond to multiple islet cell proteins.
B M Brooks-Worrell, G A Starkebaum, C Greenbaum, J P Palmer
The Journal of Immunology December 15, 1996, 157 (12) 5668-5674;
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