Do CD4 positive cytotoxic T cells damage islet beta cells in type 1 diabetes?

The mechanism by which islet ? cells are destroyed in rype I diabetes is still unknown. Because in diabetes the majoriry of T cells acîivated in vivo express CD4 and the islet p cells selectively express the HLA class II antigens needed for recognition by CD4-positive T cells, the possibility that selective damage to islet ? cells may be caused by CD4 positive cytotoxic cells was investigated. Activated T cells were clonedfrom a newly diagnosed diabetic patient, and many CD4 cytotoxic clones were detected. The clone with the highest cyrolyric capacity lysed HLA class II compatible islet cells which had been induced by interferon y and tumour necrosis factor to express class II antigens. The specificity of the lysis was demonstrated by use of histoincompatible islets, other histocompatible target cells, and blocking by anti-class-Il monoclonal antibodies. The results show that a CD4- positive T cell clone can lyse HLA class II matched islet cells; this process may be imponant in the pathogenesis of type I diabetes.