Influence of an interferon inducer on bone marrow transplant reconstitution in irradiated, leukemic mice: elevated natural killer cell numbers and improved life span.

Interferon-gamma and interferon inducers such as polyinosinic-polycytidylic acid (poly I:C) promote natural-killer (NK)-cell-mediated killing of a wide range of tumor cells both in vitro and in vivo. The aim of the present work was to administer poly I:C to irradiated, leukemic mice, both before and after syngeneic bone marrow transplant with the intent of boosting the host's natural immunity in the critical peritransplant period. Briefly, DBA/2 mice were injected with Friend-virus-induced erythroleukemia cells. After 5 days of tumor growth, some mice received daily injections of poly I:C for the next 4 days while control, leukemic mice received the saline vehicle only. All mice were then irradiated (450 R x 2 at 4-hour intervals) and transplanted 1 day following irradiation with bone marrow from age- and sex-matched, normal DBA/2 donor mice. After transplant, daily injections of poly I:C (or vehicle) continued for 8 more days. On day 9 after transplant, treated and control mice were killed, and the total cellularity, total numbers of lymphoid cells, the total numbers of NK cells (identified by the presence of an immuno-labelled, specific cell surface marker) were obtained from both the spleen and the bone marrow. Other identically treated mice subjected, however, to several additional rounds of poly I:C treatment were sampled 3 and 6 months after irradiation and bone marrow transplant. The results indicated that (a) poly I:C administered in the peritransplant period (before and after transplant) significantly increases the absolute numbers of NK cells in both the bone marrow and spleen of the transplanted host at all time intervals studied, (b) no erythroleukemic tumor cells were found, even as late as 6 months after transplant in the poly-I:C-treated hosts in spite of the fact that poly I:C treatment in this group had been terminated more than 2 months prior to tissue sampling, and (c) survival was significantly improved by pre- and posttransplant treatment with poly I:C.