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

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 sev ere GVHD, the addition of at least 1.0 x 10(6) donor spleen cells indu ced uniform acute lethal GVHD. Equivalent doses of spleen cells deplet ed of CD4(+) T cells failed to induce lethal GVHD, Allogeneic bone mar row 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, C D4(+) T cell-depleted allogeneic spleen cells prevented the progressiv e 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 p urified CD8(+) T cells were obtained by positive selection using flow cytometry. The latter cells prevented the progressive growth of the tu mor, and markedly reduced the level of tumor cells in the blood. Sorte d CD8(+) T cells facilitated the engraftment of allogeneic marrow cell s in sublethally irradiated hosts. Thus, addition of highly purified C D8(+) T cells to marrow cells provides GVL activity and facilitates en graftment without inducing severe GVHD in most recipients.