INVITRO RESISTANCE OF THE BROWN NORWAY RAT ACUTE MYELOCYTIC-LEUKEMIA (BNML) TO LYMPHOKINE-ACTIVATED KILLER ACTIVITY

In in vivo allogeneic bone marrow transplantation studies with the Bro wn Norway (BN) rat as recipient and the WAG/Rij rat as allogeneic dono r a significant graft-versus-leukemia (GVL) effect is observed. Studie s were performed to investigate whether lymphokine-activated killer (L AK) cells play a role in this GVL effect. Splenocytes from WAG/Rij and BN rats were activated in vitro by recombinant human interleukin-2 (r hIL-2) for 5-6 days. The cytolytic activity of these LAK cells was tes ted on four rat solid tumor cell lines, i.e. an ureter carcinoma, a rh abdomyosarcoma, and two lung tumors, and on leukemic cells derived fro m the BN rat scute myelocytic leukemia (BNML) and the WAG/Rij acute ly mphocytic leukemia (L4415). The panel of target cells also included th e murine cell lines P815 and YAC. Both WAG/Rij and BN LAK cells were n ot capable of lysing the leukemic cells in contrast to significant cyt olytic activity on the rat solid tumor cell lines and P815 and YAC. BN ML cells showed to be resistant to lysis by human NK cells. Phenotypic al analysis of the rat LAK population revealed a decrease in the CD4/C D8 ratio compared to the unstimulated splenocyte population. Rat LAK c ells displayed no antibody-dependent cellular cytotoxicity (ADCC) on t he leukemic cells, whereas IL-2-stimulated human peripheral blood cell s showed moderate ADCC activity on the leukemic cells. To investigate whether cytokines play a role in lysis of leukemic target cells, grade d numbers of LAK cells and leukemic cells were co-cultivated for seven days in an agar-based colony culture system. This resulted in moderat e suppression of leukemic colony formation. From the current in vitro studies it appears that the graft-versus-leukemia observed in in vivo allogeneic bone marrow transplantation studies is probably not due to a direct leukemic cell kill by LAK cells.