Prevention of recurrent diabetes in BB rats after islet transplantation by monoclonal antibody therapy.

ABSTRACT

Two immune responses imperil pancreatic islet allografts transplanted into subjects afflicted with autoimmune diabetes 1) the well-described allograft response that is mounted against tissues bearing foreign transplantation antigens and 2) a recurrence of the beta-cell-specific autoimmune process responsible for the primary disease. To define the role of autoimmune response to transplanted islets, the possibility of a rejection response must be prevented. To accomplish this in spontaneously diabetic BB rats, we induced neonatal tolerance. We found that recurrent autoimmunity in tolerant BB rats can be prevented by treatment of recipients with the monoclonal antibody OX8 (specific for cytotoxic T-lymphocytes) but not W3/25 (specific for helper T-lymphocytes). These findings provide direct evidence for the role of OX8-bearing lymphocytes in autoimmune diabetogenesis.