Adoptive transfer of anti-cytomegalovirus effect of interleukin-2-
activated bone marrow: potential application in transplantation
R Agah, BS Charak, V Chen and A Mazumder
Department of Medicine, University of Southern California, Los Angeles.
This work is a continuation of our studies that showed that interleukin- 2
(IL-2)-activated murine bone marrow (ABM) cells have potent cytotoxic
potential against murine cytomegalovirus (MCMV)-infected targets in vitro,
without loss of reconstitutive ability in vivo. Our data show that ABM
cells lyse the MCMV-infected cells in vitro, at both acute and chronic
stages of infection; this lysis is specific for the MCMV- infected cells.
ABM cells supplemented with IL-2 therapy virtually eradicated the viral
infection and prolonged the survival of MCMV- infected Balb/c mice, whether
or not they were immunocompromised by irradiation (P less than .001 in both
situations). Efficacy of ABM cells alone or IL-2 alone was less than the
combination of ABM cells and IL-2. The efficacy of combination treatment
with ABM cells and IL-2 in improving the survival of MCMV-infected mice was
comparable, whether used in a preventive or a therapeutic setting. Therapy
with ABM plus IL- 2 also prevented the reactivation of chronic MCMV
infection after irradiation. Preliminary findings indicate that Thy-1+ and
asialo GM1+ cells limited the MCMV proliferation by approximately 30% and
80%, respectively, while BM macrophages limited the proliferation of MCMV
by 100%. These results suggest that BM transplantation (BMT) with ABM cells
followed by IL-2 therapy may constitute a novel strategy to improve the
host resistance against cytomegalovirus infection after BMT.
Volume 78,
Issue 3,
pp. 720-727,
08/01/1991
Copyright © 1991 by The American Society of Hematology