EFFECT OF GVHD ON THE RECOVERY OF NK CELL-ACTIVITY AND LAK PRECURSORSFOLLOWING BMT

The mechanism by which GVHD augments the graft-versus-leukemia (GVL) e ffect of marrow transplants has not been ascertained. One possibility involves the secondary activation of natural killer (NK) cells by cyto kines released during the GVHD process. To evaluate this possibility w e have compared NK activity and lymphokine-activated killer cell precu rsor (LAKp) frequencies in serially sampled PBMC from recipients of un manipulated autologous or allogeneic marrow with and without active GV HD. NK activity recovered rapidly after BMT and was elevated during ep isodes of acute GVHD. However, NK activity did not differ between reci pients of autologous or allogeneic marrow without GVHD nor was NK acti vity increased in association with chronic GVHD. Endogenously-activate d NK cells were detected only in recipients of allogeneic marrow but t his did not correlate with GVHD status. In contrast to NK activity, LA Kp frequencies fell below the control range during the rirst 8 weeks a fter BMT. By 9-14 weeks the median LAKp frequency was normal and did n ot differ between the three groups then or later after transplant. We conclude that acute GVHD may serve to increase the lytic activity of N K cells but does not result in increased LAKp. LAKp frequencies are be low normal during the first two months after BMT, a finding not previo usly recognized from bulk culture LAK studies. The role of LAK effecto rs in GVL may involve more the degree of cellular activation rather th an the number of cells activated.