image: (A) Schematic overview of the experimental workflow. (B) Representative flow cytometry plots showing IL-2⁺, TNF-α⁺, and IFN-γ⁺ expressions of VZV-reactive CD4⁺CD45RO⁺CD154⁺ memory T cells, (C–D) Absolute numbers of VZV-reactive CD4⁺CD45RO⁺CD154⁺ memory T cells (C) and total cytokines (D) producing cells were significantly higher in BM than PB. (E) Absolute total counts of separate IL-2⁺, IFN-γ⁺, and TNF-α⁺ in VZV-reactive CD4⁺ memory T cells. (F) Absolute numbers of single, double, and triple cytokine-producing CD4⁺CD154⁺ memory T cells in PB and BM, categorized by cytokine expression (IFN-γ⁺, IL-2⁺, and TNF-α⁺). (G) Absolute numbers of polyfunctional CD4⁺CD154⁺Cyt⁺ T cells in PB and BM, defined as the sum of double and triple cytokine-producing cells.
Credit: hLife
Varicella-zoster virus (VZV), the virus behind chickenpox and shingles, can lie dormant in the body for decades before reactivating later in life. Since immune control of the virus depends heavily on CD4⁺ T cells, scientists have been trying to understand where this long-term immune memory is stored.
Now, researchers report that the bone marrow plays a central role. In a study of 19 healthy adults, they found that bone marrow contains far more VZV-reactive memory CD4⁺ T cells than peripheral blood. These cells are also more functionally potent, with a higher proportion capable of producing multiple cytokines associated with rapid and effective immune responses.
“These findings show that bone marrow is an important reservoir of VZV-reactive memory T cells and may play a key role in long-term immune protection against viral reactivation,” said Andreas Radbruch of the Deutsches Rheuma-Forschungszentrum Berlin.
Most of these cells displayed a central memory profile, though effector memory cells were also present. Together with earlier findings that VZV-specific memory T cells are enriched in the skin, the results point to a division of labor in the immune system: the skin provides local defense, while the bone marrow maintains a long-term systemic reserve.
The study offers new insight into how the body keeps VZV in check and could help guide future strategies to reduce the risk of shingles.
About Author:
Prof. Dr. Andreas Radbruch is a corresponding author of this study and the director emeritus of the German Rheumatism Research Centre (DRFZ), a Leibniz institute. His work focuses on the molecular basis of immunological memory, long-lived plasma cells, control of autoimmunity, cytokine gene expression, flow cytometry, and cell sorting.
Journal
hLife
Article Title
Polyfunctional varicella-zoster virus–reactive memory CD4⁺ T cells reside in human bone marrow
Article Publication Date
9-Apr-2026