T-cell response to proinsulin and insulin in type 1 and pretype 1 diabetes.
Insulin-dependent diabetes mellitus (IDDM) results from the selective destruction of pancreatic beta cells by a T cell-mediated autoimmune process. Insulin and proinsulin are the only known beta 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.
Dubois-LaForgue
D
D
INSERM U342, Hôpital Saint-Vincent de Paul, Paris, France.
Carel
J C
JC
Bougnères
P F
PF
Guillet
J G
JG
Boitard
C
C
D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000276:immunology*; D008213:Lymphocyte Activation; D008875:Middle Aged; D011384:Proinsulin / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D001323:Autoantibodies; D006684:HLA-DR Antigens; D007328:Insulin; D011384:Proinsulin