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

Nowadays there is compelling evidence for immunoregulation by T cells. Recently, we showed that so-called 'anergic' T cells are not functionally inert but can act as regulatory cells by actively suppressing other T cell responses. We now show that 'anergic' T cells mediate this suppressive effect via modulation of the T-cell activating capacity of the antigen-presenting cell (APC). Upon removal of the 'anergic' T cells, the suppressive APC phenotype persisted, indicating that 'anergic' T cells conditioned the APC to become a mediator of T cell suppression. The inhibitory signal delivered by 'anergic' T cells depended on the presence of the cognate ligand for the 'anergic' T cell, and appeared to be dominant since previously activated APC were rendered inhibitory as well. These findings imply that APC upon cross-talk with T cells can adopt distinct functional phenotypes ranging from T-cell stimulatory to T-cell suppressive. The contribution of 'anergic' T cells to the functional tuning of APC offers an explanation for the maintenance of 'anergic' T cells in the repertoire, and for their role in immunoregulation.