Cellular interactions in marrow-grafted patients. I. Impairment of cell-mediated lympholysis associated with graft-vs-host disease and the effect of interleukin 2.

Forty patients with hematologic malignancy or aplastic anemia were given allogeneic marrow after conditioning with high-dose cyclophosphamide alone or in combination with total body irradiation. Between 28 and 3857 days after transplantation, their peripheral blood mononuclear leukocytes were tested for reactivity in indirect cell-mediated lympholysis against normal leukocytes from unrelated individuals, and the results were compared to those with cells from their healthy marrow donors. An impairment of cell-mediated lympholysis was found with cells from most patients with acute and chronic graft-vs-host disease (GVHD) whereas cells from most short-term and long-term patients without GVHD had cell-mediated lympholysis reactivity comparable to that of cells from the marrow donors. When interleukin 2 was added to the mixed leukocyte cultures during the sensitization phase, the impaired cell-mediated immunity of cells from most short-term patients with acute GVHD, but not that of cells from most patients with chronic GHVD, could be restored to normal levels. These results suggest the impairment of cell-mediated immunity seen in cells of short-term patients with acute GVHD is attributable to helper cell defects or to ineffective communication between antigen-presenting cells and helper T cells. The impairment in cell-mediated immunity seen in patients with chronic GVHD, however, may reside on the effector cells (or their precursors) or may be due to the presence of suppressor cell activity.