Transfer of type 1 (insulin-dependent) diabetes mellitus associated autoimmunity to mice with severe combined immunodeficiency (SCID).
Pancreatic beta-cell destruction and development of Type 1 (insulin-dependent) diabetes mellitus are associated with circulating islet cell antibodies. Mice with severe combined immunodeficiency (SCID mice) were reconstituted with peripheral blood mononuclear cells from Type 1 diabetic patients, one who was antibody positive and one antibody negative, and from healthy individuals. Reconstituted mice were subsequently immunized with rat islets in incomplete Freunds adjuvant or adjuvant alone. Seventeen mice received peripheral blood mononuclear cells obtained at three different time points from the islet cell antibody positive patient. Before immunization with rat islets two mice developed antibodies to glutamic acid decarboxylase, a major target for antibodies in Type 1 diabetes, whereas none were positive for cytoplasmic islet cell antibodies. Following immunization with rat islets, glutamic acid decarboxylase antibodies were detected by immunoprecipitation in three additional mice, two of which also became positive for cytoplasmic islet cell antibodies. Of 22 mice which received peripheral blood mononuclear cells from either the islet cell antibody negative patient (n = 5) or from two healthy individuals (n = 17), none were positive for islet cell autoantibodies before or after immunization. None of the islet cell antibody positive mice became hyperglycaemic, showed impaired glucose tolerance or islet cell damage when studied 40 days after immunization (i.e. 100 days after reconstitution). In conclusion these results show that human B lymphocytes producing diabetes-associated autoantibodies can be transferred to SCID mice and remain antigen sensitive, but also that autoantibodies alone are not sufficient to induce beta-cell destruction.
Petersen
J S
JS
Hagedorn Research Institute, Gentofte, Denmark.
Marshall
M O
MO
Baekkeskov
S
S
Hejnaes
K R
KR
Høier-Madsen
M
M
Dyrberg
T
T
D000818:Animals; D001323:Autoantibodies / Q000008:administration & dosage / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005968:Glutamate Decarboxylase / Q000097:blood / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D016219:Immunotherapy, Adoptive; D007515:Islets of Langerhans / Q000276:immunology*; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D016513:Mice, SCID
D001323:Autoantibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C024211:islet cell antibody; D005968:Glutamate Decarboxylase