'Anergic' T cells modulate the T-cell activating capacity of antigen-presenting cells

Nowadays there is compelling evidence for immunoregulation by T cells. Rece ntly, we showed that so-called 'anergic' T cells are not functionally inert but can act as regulatory cells by actively suppressing other T cell respo nses. We now show that 'anergic' T cells mediate this suppressive effect vi a modulation of the T-cell activating capacity of the antigen-presenting ce ll (APC). Upon removal of the 'anergic' T cells, the suppressive APC phenot ype persisted, indicating that 'anergic' T cells conditioned the APC to bec ome a mediator of T cell suppression. The inhibitory signal delivered by 'a nergic' T cells depended on the presence of the cognate ligand for the 'ane rgic' T cell, and appeared to be dominant since previously activated APC we re rendered inhibitory as well. These findings imply that APC upon cross-ta lk with T cells can adopt distinct functional phenotypes ranging from T-cel l stimulatory to T-cell suppressive. The contribution of 'anergic' T cells to the functional tuning of APC offers an explanation for the maintenance o f 'anergic' T cells in the repertoire, and for their role in immunoregulati on. (C) 2000 Academic Press.