T Cell Autoreactivity in the Transplant Milieu

Autoreactive T cell responses in autoimmune disease are directed to tissue antigens but differ from allospecific T cells in several important respects, reflecting the circumstances of their selection, activation and expansion in vivo. Both genetic and acquired traits conspire to generate autoreactive effector cells that are refractory to normal control mechanisms, resulting in persistent and deleterious immunity to tissue antigens. When these same tissue antigens are reintroduced into an autoimmune setting, such as with pancreas or islet transplantation into a type 1 diabetic individual, the potential for recurrent activation of the underlying effector memory response presents a therapeutic challenge.