Augmentation of the graft-versus-host reactivity of parental cells by the addition of small doses of alloantigen-activated T cells.

Abstract

The direct action of alloantigen-activated T cells on the generation of graft-versus-host (GVH)-reactive T cells from their precursors was investigated in an in vivo system by the popliteal lymph node enlargement assay using normal and macrophage-depleted F1 hybrid rats. When very small numbers of alloantigen-activated parental T cells were inoculated in the foot-pads of F1 hosts 24 hr prior to the parental cell inoculum, a significant increase of the GVH reactivity of peripheral T cells was observed within the draining node in normal F1 rats and in F1 hosts in which an active participation of endogenous cells was greatly minimized. Moreover, a similar augmenting action of alloantigen-activated T cells was found in the thymocyte-GVH reaction, which was much higher than that of peripheral T cells when their stimulation indices were compared. These phenomena were produced by the addition of any of two different RT 1 species of alloantigen-activated T cells that were restimulated with F1 host-specific or nonspecific third-party alloantigen within the region of the assay, suggesting the importance of the restimulation of the alloantigen-activated T cell inoculum. A simultaneous injection of bacterial lipopolysaccharide had a cumulative effect on the augmenting action of alloantigen-activated T cells on the thymocyte GVH reaction. This study indicates that the preexistence of alloantigen-activated T cells at the assay site causes precocious maturation and proliferation of immature thymocytes, which allows them to function as GVH-reactive T cells in the periphery in vivo; it also suggests the presence of a serial stimulation network through T-T interactions in connection with macrophage-T-cell synergism and the interleukins.