Bovine and human NPH insulins as T cell immunogens.
The aim of this study was to assess the immunocompetence of T cells from patients with poorly controlled diabetes with respect to Candida albicans antigen and to compare the relative immunogenicity of human insulin, bovine insulin and protamine at the T-cell level during 6 months treatment with human or bovine NPH insulins. T-cell proliferation was measured in vitro in response to C. albicans, bovine and human insulin, bovine and human NPH and protamine in 17 patients with newly-diagnosed type 1 (insulin-dependent) and 12 with poorly-controlled type 2 (non-insulin-dependent diabetes) before and after 0.5, 1, 3 and 6 months of treatment with either bovine or human NPH insulin. The following results were found: Baseline responses to C. albicans (as a recall antigen) were similar for patients and controls despite marked hyperglycaemia in the patients. No patient had a response greater than mean + 2 S.D. of controls to human or bovine insulin before starting treatment, or had insulin autoantibodies. Treatment with human NPH insulin did not induce T-cell responses to human or bovine insulin, but 3/13 (23%) patients treated with bovine NPH responded to bovine and human insulin after 6 months, of whom one responded exclusively to human. In contrast, 6 (46%) bovine and 3 (19%) human NPH-treated patients responded to protamine. It was concluded that there is no evidence of T-cell immunosuppression in poorly-controlled diabetes or of T-cell autoimmunity to insulin in newly-diagnosed type 1 diabetes. Treatment with bovine NPH insulin immunizes T cells to insulin, but human NPH does not.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Immunology, University Hospital, Queen's Medical Centre, Nottingham, UK.
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Gregory
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Tattersall
D000293:Adolescent; D000328:Adult; D000818:Animals; D000946:Antigens, Fungal / Q000276:immunology; D001323:Autoantibodies / Q000097:blood; D002176:Candida albicans / Q000276:immunology; D002417:Cattle; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000276:immunology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000276:immunology; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D016130:Immunophenotyping; D007336:Insulin, Isophane / Q000276:immunology* / Q000627:therapeutic use; D007515:Islets of Langerhans / Q000276:immunology; D008213:Lymphocyte Activation; D008875:Middle Aged; D011479:Protamines / Q000494:pharmacology; D011994:Recombinant Proteins / Q000276:immunology / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D000946:Antigens, Fungal; D001323:Autoantibodies; D006684:HLA-DR Antigens; D011479:Protamines; D011994:Recombinant Proteins; C024211:islet cell antibody; D007336:Insulin, Isophane