Kinetics of T cell activation in acute and chronic forms of murine graft-versus-host disease

Induction of graft-vs-host disease (GVHD) in the parent-into-F1 model is dependent on the presence of T cells in the donor inoculum. Although in vivo activation of donor T cells in response to F1 alloantigens is thought to be critical to GVHD induction, direct evidence of activated donor T cells has been lacking in this model. In the present study, spleen cells from acute or chronic GVHD mice were studied for evidence of T cell activation at multiple intervals early after GVHD induction. Spleen cells from both acute and chronic GVHD mice exhibited striking elevations in spontaneous proliferation and IL-2 production, which were maximal 24 to 48 h after GVHD induction. Persistent lower levels of spontaneous in vitro activity were observed for spleen cells from mice tested 7 to 9 days after GVHD induction. In both forms of GVHD, increased spontaneous proliferation and IL-2 production were dependent on the presence of donor CD4⁺ T cells. These results strongly support the presence of activated donor T cells in vivo. Furthermore, these data imply that despite the significant differences in outcome, acute and chronic GVHD share a common early event.