Natural killer function following allogeneic bone marrow transplantation: very early reemergence but strong dependence of cytomegalovirus infection

Natural killer (NK) cell function was followed sequentially after allogeneic bone marrow transplantation (BMT) using three approaches: (1) chromium-release assay with purified mononuclear effector cells, (2) chromium-release assay with whole blood effectors, and 3) enumeration of lymphocytes bearing the NK-associated antigen NKH-1 (N901). The two latter methods enabled us to demonstrate a very early reappearance (at day 4 posttransplant) of pre-NK cells, which after interferon-alpha enhancement effectively lysed K562 cells and carried the NKH-1 antigen. During the first month NK function steadily increased, and at day 28 activated NK cells, which lysed the otherwise resistant P815 cell line, could be demonstrated concomittant with a substantial over-shoot in the proportion of NKH-1+ cells. Furthermore, the increase in NK lysis was more pronounced in patients with cytomegalovirus (CMV) infections (primary or reactivated). In contrast, the presence of graft-versus-host (GVH) disease did not associate with consistent changes in the NK parameters measured here. After the first month of increase, NK declined reaching levels near those observed in their respective bone marrow donors at day 90. These data demonstrate a surprisingly early recovery after allogeneic BMT, which can largely be related to external factors among which CMV seems to be a prime candidate.