Donor cell persistence and activation-induced unresponsiveness of peripheral CD8(+) T cells

We studied the impact of the duration of donor cell persistence on CD8(+) T cell responsiveness after adoptive transfer of antigen-expressing lymphoid cells. Naive or immunized female mice were treated by adoptive transfer of spleen cells from mice ubiquitously expressing a lymphocytic choriomeningi tis virus-derived cytotoxic T lymphocyte (CTL) epitope (gp33-41) either alo ne or in combination with the male H-Y antigen providing additional antigen ic CTL and T helper cell determinants. Low doses of male spleen cells (or s orted B cells) primed CTL, while high doses of the same cells rendered them unresponsive. CTL unresponsiveness induced by high numbers of male spleen cells was dependent upon prolonged persistence of antigen-expressing donor cells. Unresponsive CTL reverted to a state of activation when the duration of donor cell chimerism was limited. Memory CTL could be rendered unrespon sive if antigen-expressing donor cells were allowed to persist. These resul ts suggest that, irrespective of the type of antigen-presenting cell and th e functional state of the responding T cell, activation and unresponsivenes s can represent two different outcomes critically determined by quantitativ e and kinetic differences of antigen persistence.