Adoptive transfer of anti-cytomegalovirus effect of interleukin-2-activated bone marrow: potential application in transplantation.
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.
Agah
R
R
Department of Medicine, University of Southern California, Los Angeles.
Charak
B S
BS
Chen
V
V
Mazumder
A
A
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000276:immunology*; D016026:Bone Marrow Transplantation; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000628:therapy; D005260:Female; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000494:pharmacology* / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000276:immunology
D007376:Interleukin-2