In Vitro Transmission of HCMV between Fibroblasts and Peripheral Blood Leukocytes in the Presence of IL-4.

Abstract

Summary: We demonstrated transmission of human cytomegalovirus (HCMV) from the human lung fibroblast MRC-5 to peripheral blood leukocytes (PBLs). mRNA of the HCMV immediately early (IE) antigen was detected in PBLs cultured with IL-2 or IL-2+ IL-4 that made direct contact with HCMV-infected MRC-5, whereas it was not detected in PBLs prevented from making cell-to cell contact. However, mRNA of HCMV IE was not detected in PBLs cultured with IL-2 and IFN gamma that made direct contact with HCMV-infected MRC-5. Transmission of the pp65 antigen was increased in culture medium containing IL-4. At a higher viral infection titer, cell-free HCMV infected adherent PBLs cells. The subset, which did not adhere, did not infect cell-free viruses even at a very high multiplicity of infection. Moreover, the adhered subset of PBLs infected with HCMV was able to transmit HCMV to non-infected fibroblasts. Our results suggest that cell-to-cell contact (when PBLs make direct contact with HCMV-infected cells) is important in the mechanism of HCMV transmission and that the adherent cells of PBLs are one of the most important vehicles for HCMV infection. Moreover, we suggest that type 2 cytokines such as IL-4 enhance the transmission of HCMV to PBLs.

Risk assessment of human cytomegalovirus infection in solid organ transplantation: Insight into CD4+ T cell subsets

“…Thus, as a carrier, the monocyte is likely to spread the virus into various organs. 4,43,44,52,53 After antigenic stimulation in healthy seropositive individuals, no responses were observed for IL-4 secretion alone, but its secretion was often accompanied by IFN-γ or IL-17. This motivates the hypothesis that Th2 responses could be beneficial when combined with Th1 or Th17 cells.…”

“…Some studies hypothesized that Th2 immunity may exacerbate virus infection by reducing Th1 responses or may impact HCMV transmission to monocytes by IL‐4 cytokine. Thus, as a carrier, the monocyte is likely to spread the virus into various organs 4,43,44,52,53 …”

Decreased frequency of Th22 cells and IL-22 cytokine in kidney transplant patients with active cytomegalovirus infection

“…Th1 cells producing TNF-α, IFN-γ, and IL-2 were reduced during HCMV active infection in Solid Organ Transplant (SOT) recipients, e.g., kidney and liver [ 12 – 15 ]. In contrast, evidence shows that Th2 cells producing IL-4 may exacerbate infection by reducing Th1 immunity or transmitting HCMV to monocytes [ 9 , 13 , 14 , 16 , 17 ]. The Tfh cells producing IL-21 are related to HCMV control in SOT patients via increasing the neutralizing and IgG antibodies.…”