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T-Cell Response to Proinsulin and Insulin in Type 1 and Pretype 1 Diabetes

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Abstract

Insulin-dependent diabetes mellitus (IDDM) results from the selective destruction of pancreatic β cells by a T cell-mediated autoimmune process. Insulin and proinsulin are the only known β cell-specific autoantigens. Using short-term cultures of freshly isolated peripheral blood mononuclear cells, we evaluated T-cell responses to proinsulin and to insulin in IDDM patients and individuals at risk for IDDM. A proliferative T-cell response to proinsulin was observed in only 2 of 26 recent-onset IDDM subjects and 2 of 12 long-standing IDDM subjects and was associated with a proliferative response to insulin. In contrast, 5 of 13 islet cell autoantibody-positive first-degree relatives of IDDM patients showed a proliferative response to proinsulin alone, 3 of 13 to insulin alone, and 1 of 13 to both insulin and proinsulin. Overall, 9 of 13 ICA-positive first-degree relatives responded to either proinsulin or insulin. We observed an inverse relationship between antiinsulin antibodies and T-cell responses to insulin in ICA-positive first-degree relatives but not in long-standing IDDM patients. Our data indicate that proinsulin is a major antigen in IDDM and, further, illustrate the difference between the autoimmune response to insulin and the immune response to exogenous insulin.

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Authors and Affiliations

  1. INSERM U342, Hôpital Saint-Vincent de Paul, 82 Avenue Denfert-Rochereau, 75014, Paris, France

    Danièle Dubois-LaForgue, Jean-Claude Carel, Pierre-François Bougnères, Jean-Gérard Guillet & Christian Boitard

  2. Diabetology Unit, Department of Clinical Immunology, Hôpital Necker, 161 rue de Sèvres, 75015, Paris, France

    Danièle Dubois-LaForgue & Christian Boitard

  3. Pediatric Endocrinology Unit, Hôpital Saint-Vincent de Paul, 75014, Paris, France

    Jean-Claude Carel & Pierre-François Bougnères

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  1. Danièle Dubois-LaForgue
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  3. Pierre-François Bougnères
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  4. Jean-Gérard Guillet
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  5. Christian Boitard
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Dubois-LaForgue, D., Carel, JC., Bougnères, PF. et al. T-Cell Response to Proinsulin and Insulin in Type 1 and Pretype 1 Diabetes. J Clin Immunol 19, 127–134 (1999). https://doi.org/10.1023/A:1020558601175

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