Suppression of normal human hematopoiesis by cytomegalovirus in vitro

Human cytomegalovirus (HCMV) infection is associated with marrow suppression in immunocompromised patients. To examine the mechanism(s) underlying this suppression, the effect of a laboratory strain of HCMV (AD169) and a clinical isolate of HCMV on colony formation by normal human marrow (BMC) hematopoietic progenitors in the presence and/or absence of monocyte/macrophages (MO) and T cells was studied. Direct addition of HCMV at multiplicity of infection (MI) of 0.1 to 5 to BMC produced dose-dependent inhibition of colony forming unit-mix (CFU-Mix) (30-82%), CFU granulocyte, macrophage (CFU-GM) (15-98%), and burst forming unit-erythroid (BFU-E) (23-86%); no consistent effect of CFU-erythroid (CFU-E) was noted. This inhibition occurred both with the direct addition of HCMV to the culture plates as well as by the preincubation of BMC with HCMV followed by washing of the cells; significant inhibition (p < 0.01) of colony formation occurred after 1 hour of incubation at MI of 5. No suppression of colony formation occurred when UV-irradiated virus was used. The inhibitory effect of HCMV was reduced when MO and T cells were removed prior to exposure of marrow to virus at MI of 1 to 5. At MI of 20, however, HCMV suppressed colony formation by BMC depleted of MO and T cells by about 40%. Coculture of autologous or allogeneic T cells, but not MO, exposed to HCMV with intact or depleted marrow resulted in inhibition of CFU-Mix (51%), CFU-GM (40%), and BFU-E (37%). The inhibitory effect of virus-exposed T cells did not appear to be mediated through a soluble factor. T cells expressing CD8 antigen were most active in this process; natural killer (NK) cells were not active. These results suggest that the suppressive effect of HCMV on hematopoiesis may be mediated in part through T lymphocytes.