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-de pendent) diabetes mellitus are associated with circulating islet cell antibodies. Mice with severe combined immunodeficiency (SCID mice) wer e reconstituted with peripheral blood mononuclear cell from Type 1 dia betic patients, one who was antibody positive and one antibody negativ e, and from healthy individuals. Reconstituted mice were subsequently immunized with rat islets in incomplete Freunds adjuvant or adjuvant a lone. Seventeen mice received peripheral blood mononuclear cells obtai ned at three different time points from the islet cell antibody positi ve patient. Before immunization with rat islets two mice developed ant ibodies to glutamic acid decarboxylase, a major target for antibodies in Type 1 diabetes, whereas none were positive for cytoplasmic islet c ell 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 is let cell antibodies. Of 22 mice which received peripheral blood mononu clear cells from either the islet cell antibody negative patient (n = 5) or from two healthy individuals (n = 17), none were positive for is let cell autoantibodies before or after immunization. None of the isle t cell antibody positive mice became hyperglycaemic, showed impaired g lucose tolerance or islet cell damage when studied 40 days after immun ization (i.e. 100 days after reconstitution). In conclusion these resu lts show that human B lymphocytes producing diabetes-associated autoan tibodies can be transferred to SCID mice and remain antigen sensitive, but also that autoantibodies alone are not sufficient to induce beta- cell destruction.