Suppression of autologous mixed leukocyte reaction in type 1 diabetes mellitus by in vivo-activated T lymphocytes.

In vivo-activated interleukin 2 receptor-positive T lymphocytes (Tac cells) are demonstrable and the autologous mixed leukocyte reaction (AMLR) is impaired in several autoimmune diseases, including type 1 insulin-dependent diabetes mellitus (IDDM). We investigated AMLR in greater detail, together with possible relationships between AMLR and Tac lymphocytes in IDDM. Coculture experiments with HLA identical patient-healthy sibling pairs revealed that both responder and stimulator cells of diabetic patients function abnormally in AMLR. Suppressive Tac lymphocytes among responder T cells seemed to impair their proliferation. The removal of Tac cells by immunomagnetic beads led to a striking enhancement of proliferation, while the restoration of AMLR cultures with enriched Tac cells was accompanied by a diminished response. The reasons for the poor stimulatory capacity of patient cells are at present unknown but may be due to altered function and/or structure of HLA-DR molecules.