α-Galactosylceramide-expanded virtual memory CD8+ T cells confer protection against a broad range of pathogens

作者：Jia-Xun Xie, Donglin Li, Meng-Chih Lai, Yu-Ling Su, Chi Tai, Ching-Chun Wang, Jr‐Shiuan Lin · 发表于：Frontiers in Immunology · 年份：2026 · DOI：10.3389/fimmu.2026.1799271 · 研究领域：Immune Cell Function and Interaction、T-cell and B-cell Immunology、Immunotherapy and Immune Responses

α-Galactosylceramide (α-GalCer) treatment of animals is a well-established model to investigate the beneficial roles of invariant natural killer T (iNKT) cells in anti-infection and anti-tumor immunity. We previously found that α-GalCer treatment expands not only iNKT cells but also a group of antigen-inexperienced memory-like innate virtual memory CD8 + T (CD8 + T VM ) cells. With the bystander protective potential of CD8 + T VM cells, their roles in α-GalCer-mediated immunity against infection remain largely unexplored. Here, we reported that α-GalCer treatment conferred protection against systemic, enteric, and pulmonary bacterial infections, as well as pulmonary viral infection. This protection persisted after iNKT cells had diminished and coincided with sustained expansion of CD8 + T VM cells. Adoptive transfer of α-GalCer-expanded CD8 + T VM cells one day before infection significantly decreased bacterial and viral burdens. Mechanistically, α-GalCer treatment activated iNKT cells to produce IL-4, which subsequently expanded the number of CD8 + T VM cells that were capable of producing TNF-α and IFN-γ. But the ability of each individual CD8 + T VM cell to produce these cytokines was not enhanced. Lung-localized CD8 + T VM cells were the primary contributors to α-GalCer-expanded CD8 + T VM cells in the lung. α-GalCer-expanded CD8 + T VM cells can reduce pulmonary viral titer in the host in a TNF-α-dependent manner in the absence of IFN-γ signaling. Together, these finding...