THE ROLE OF PURIFIED CD8(+) T-CELLS IN GRAFT-VERSUS-LEUKEMIA ACTIVITY AND ENGRAFTMENT AFTER ALLOGENEIC BONE-MARROW TRANSPLANTATION

The ability of highly purified CD8(+) T cells to mediate GVL activity and facilitate engraftment of allogeneic bone marrow cells was studied in the C57BL/Ka --> BALB/c mouse strain combination, Splenic CD8(+) T cells were enriched by depletion of CD4(+) T cells by ''panning'' or purified by positive selection by cell sorting, Although C57BL/Ka bone marrow cells reconstitute lethally irradiated BALB/c mice without severe GVHD, the addition of at least 1.0 x 10(6) donor spleen cells induced uniform acute lethal GVHD. Equivalent doses of spleen cells depleted of CD4(+) T cells failed to induce lethal GVHD, Allogeneic bone marrow cells alone failed to mediate antitumor activity against the BCL(1) B cell leukemia/lymphoma as compared with syngeneic bone marrow and spleen cell injections. Despite the inability to induce severe GVHD, CD4(+) T cell-depleted allogeneic spleen cells prevented the progressive growth of the BCL(1) tumor, and eliminated BCL(1) idiotype-positive tumor cells in the blood, In order to determine whether CD8(+) T cells can prevent tumor growth in the absence of other spleen cell subsets, such as NK cells, that are present in the CD4(-) population, highly purified CD8(+) T cells were obtained by positive selection using flow cytometry. The latter cells prevented the progressive growth of the tumor, and markedly reduced the level of tumor cells in the blood. Sorted CD8(+) T cells facilitated the engraftment of allogeneic marrow cells in sublethally irradiated hosts. Thus, addition of highly purified CD8(+) T cells to marrow cells provides GVL activity and facilitates engraftment without inducing severe GVHD in most recipients.