Perforin-independent regulation of dendritic cell homeostasis by CD8(+) T cells in vivo: implications for adaptive immunotherapy

We investigated here the effects of perforin on CTL responses during intera ction of dendritic cells (DC) with cytotoxic T lymphocytes in vivo. Using M HC class I tetramers complexed with the immunodominant CTL epitope of the l ymphocytic choriomeningitis virus glycoprotein (LCMV-GP33), we followed the kinetics of DC-induced CTL responses. GP33-presenting DC induced rapid pri mary expansion of both perforin-competent and -deficient CTL with similar k inetics. Secondary CTL responses in perforin-deficient and normal control m ice after DC-booster immunization were more rapid than the primary response s, but never reached the high initial levels, suggesting that reactivated m emory CTL eliminated the antigen-presenting DC and thereby limited the boos ter effect. Whereas killing of DC in vitro was strictly dependent on perfor in, elimination of GP33-presenting DC by CTL in vivo was largely independen t of perforin and Fas. Taken together, these results suggest that control o f DC homeostasis by CTL, i. e. elimination of DC by the effector cells they had elicited, is controlled via multiple and probably redundant signals an d represents an important fail-safe mechanism to avoid exaggerated CTL resp onses.