Immunospecific depletion of graft-versus-host-reactive lymphocytes using sensitized syngeneic initiator T lymphocytes.

We investigated a model of a lethal graft-versus-host (GVH) reaction with the aim of depleting donor spleen cells of immunospecific GVH-reactive lymphocytes. In previous studies of the recruitment of effector T lymphocytes by sensitized syngeneic initiator T lymphocytes (ITLs) we found, using a local GVH reaction, that precursors of specific GVH-reactive lymphocytes were recruited to a draining lymph node. In this study, adult F1 hybrid mice were lethally irradiated and reconstituted with 2 x 10(6) syngeneic bone marrow cells and varying numbers of spleen cells from parental strain mice. To deplete donor spleen cells of GVH-reactive lymphocytes, parental strain mice were given injections in the hind footpads 6 days earlier of syngeneic ITLs that had been sensitized in vitro against allogeneic fibroblasts. We found that injection of ITLs sensitized against the relevant allogeneic antigens led to a marked decrease in the specific GVH potential of donor spleen cells. These findings show that GVH-reactive lymphocytes can be depleted selectively by activating their recruitment to particular lymph nodes, using syngeneic ITLs.