A distinct population of nonphagocytic and low level CD4+ null lymphocytes produce IFN-alpha after stimulation by herpes simplex virus-infected cells
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Updated: Aug 9, 2026

Generation of Multivirus-specific T Cells to Prevent/treat Viral Infections after Allogeneic Hematopoietic Stem Cell Transplant
Published on: May 27, 2011
K Sandberg1, P Matsson, G V Alm
1Department of Veterinary Microbiology, Swedish University of Agricultural Sciences, Uppsala.
Abstract:
Human PBMC were stimulated for 6 h in vitro by HSV or Sendai virus (SV) and analyzed by flow cytometry. IFN-alpha producing cells (IPC) were identified through their content of IFN-alpha mRNA by in situ hybridization using a 35S-labeled IFN-alpha 2 cRNA probe. The IPC induced by HSV-infected WISH cells lacked capacity to adhere to and phagocytose latex particles. The induction of IFN-alpha by free infectious SV occurring in monocytes was abolished by phagocytosis of latex particles present in the cultures during the induction period. Such latex particles actually enhanced the IFN-alpha response induced by glutaraldehyde-fixed HSV- or SV-infected WISH cells or by free intact HSV. The HSV-induced IPC did not express the CD14 Ag expressed on monocytes. Cell sorting was performed on HSV-induced PBMC labeled with phycoerythrin-conjugated anti-CD3 and FITC-conjugated anti-CD4 mAb. A small population consisting of 1.4% of all PBMC, which was CD3- but expressed low but significant levels of CD4, contained the majority of the IPC with a 50-fold increase of their frequency. This cell population had a forward- and right-angle light scatter different from typical monocytes/macrophages. The results therefore further delineate IPC among PBMC into monocytes, being stimulated by viruses such as SV. Another distinct population of infrequent but highly efficient IPC, tentatively designated natural IFN-alpha producing cells, is activated by stimuli such as HSV.
Insights
Human peripheral blood mononuclear cells (PBMC) produce interferon-alpha (IFN-alpha) when exposed to viruses. Two distinct cell types were identified: monocytes responding to Sendai virus (SV) and a novel population responding robustly to herpes simplex virus (HSV).
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Interferon-alpha (IFN-alpha) is crucial for antiviral defense.
- Identifying specific cell populations responsible for IFN-alpha production is key to understanding immune responses.
- Human peripheral blood mononuclear cells (PBMC) are a primary source of IFN-alpha.
Purpose of the Study:
- To characterize and differentiate the cells within human PBMC that produce IFN-alpha upon viral stimulation.
- To investigate the influence of different viral stimuli (Herpes Simplex Virus - HSV, Sendai Virus - SV) and phagocytic activity on IFN-alpha production.
- To identify novel cell populations involved in IFN-alpha induction.
Main Methods:
- PBMC stimulation with HSV or SV for 6 hours.
- Flow cytometry analysis.
- In situ hybridization to detect IFN-alpha mRNA.
- Phagocytosis assays using latex particles.
- Cell sorting based on CD3 and CD4 markers.
- Analysis of CD14 antigen expression.
Main Results:
- Monocytes produced IFN-alpha in response to SV, but this was inhibited by latex particle phagocytosis.
- Latex particles enhanced IFN-alpha production induced by fixed virus or intact HSV.
- HSV-induced IFN-alpha producing cells (IPC) did not express CD14.
- A distinct, infrequent CD3-, CD4-low PBMC population (1.4% of total) showed a 50-fold higher frequency of IPC and distinct light scatter properties, termed natural IFN-alpha producing cells (NIPC).
Conclusions:
- Human PBMC contain at least two distinct populations of IFN-alpha producing cells.
- Monocytes are stimulated by viruses like SV, with their IFN-alpha production modulated by phagocytosis.
- A novel, highly efficient population of NIPC is activated by stimuli such as HSV, representing a significant finding in innate immunity research.
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