The Effect of T Cell Depletion from Spleen Cell Allografts on Graft-versus-Host Disease and Long-Term Immune Reconstitution in H-2 Haplotype-Identical Murine Combinations

Abstract

Graft-versus-host disease (GVHD) and states of immune reconstitution in allogeneic chimera mice across minor histocompatibility antigens were analyzed in excess of 9 months after injecting AKR/JSea (AKR) spleen cells into irradiated C3H/HeSlc (OH) mice.When T cell-depleted AKR spleen cells were used as inoculum cells, neither graft failure nor GVHD was seen for 9 months postgrafting in the OH mice irradiated with 660 rad or more.In an AKR - C3H (850 rad) model, Thy1.1 + or L3T4 + T cell depletion from donor AKR spleen cells abolished both acute and chronic GVHD in lethally irradiated C3H mice.Lyt2 + T cell depletion, however, resulted in acute and chronic GVHD in more than half of the recipient OH mice.Moreover, actual existence of donor(AKR)-type T cells with L3T4 phenotype, but not Lyt2 phenotype, was always observed in the spleen of the OH mice suffering from acute GVHD. In addition, the C3H mice that were irradiated with 850 rad, grafted with AKR spleen cells depleted of Lyt2.1 + T cells, escaped from acute GVHD and survived for more than 10 mo postgrafting, showed impaired activities of immune responses such as delayed footpad reaction to sheep red blood cells, antibody production tested by IgM plaque forming cells and reactivity to an intracellular bacterium Listeria monocytogenes as compared with the C3H mice reconstituted with syngeneic C3H spleen cells or Thy1.1 + or L3T4 + T cell-depleted AKR spleen cells. These results suggest that L3T4 + T cells, rather than Lyt2 + T cells, contained in the grafted cells not only cause acute GVHD but also a long-term immunodeficient state (chronic GVHD) in recipient mice in the H-2-identical murine combinations examined here.