Prevention of CMV-induced myelosuppression by anti-CMV antibodies: an in vitro model.
Pathogenesis of cytomegalovirus (CMV)-induced myelosuppression is not clearly understood and could be related to a direct toxic effect on the marrow progenitors and/or an alteration of the marrow environment. Myeloid progenitors (granulocyte-macrophage colony-forming units, CFU-GM) were not affected by incubation with increasing titers of CMV (10-10(5) plaque-forming units [pfu]/ml) during 2-6 h. By contrast, using the blast colony-forming cell (Bl-CFC) assay, we confirmed that CMV induced myelosuppression through an alteration of the marrow-derived stromal layer. Using this experimental model, we compared the capacity of nonspecific human immunoglobulins (IgG), specific polyclonal anti-CMV IgG, and a human monoclonal anti-CMV IgG to prevent the myelosuppressive effect of 10(4) pfu/ml of CMV. Specific anti-CMV IgG (polyclonal or monoclonal) at the concentration of 10 micrograms/ml were able to prevent the CMV-induced myelosuppressive effect, whereas nonspecific human IgG was not effective in this model. Our results suggest that 1) CMV-induced myelosuppression is related to an alteration of the marrow microenvironment, 2) specific monoclonal and polyclonal anti-CMV IgG prevent this myelosuppressive effect in vitro, and 3) human monoclonal anti-CMV IgG could be useful in vivo in the immunoprophylaxis of CMV infections.
Bron
D
D
Institut Jules Bordet, Brussels, Belgium.
Lagneaux
L
L
Delforge
A
A
Otte
C
C
Snoeck
R
R
Stryckmans
P
P
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D000914:Antibodies, Viral / Q000276:immunology / Q000627:therapeutic use*; D001854:Bone Marrow Cells; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000276:immunology* / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000503:physiopathology* / Q000517:prevention & control; D006098:Granulocytes / Q000187:drug effects / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000502:physiology; D008264:Macrophages / Q000187:drug effects / Q000502:physiology
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D007074:Immunoglobulin G