Defining molecular circuits of CD8+ T cell responses in tissues during latent viral infection

• DOI: 10.1084/jem.20242078
• Publication Date: 2025-05-19T13:53:56Z
• Authors: Endi K. Santosa; Jennifer M. Zhang; John C. Sauter; Mariah E. Lee; Brandon D. Ng; Sigrun V. Stulz; Meril Takizawa; Simon Grassmann; Orr-El Weizman; Nicholas M. Adams; Ronan Chaligné; Annette Oxenius; Georg Gasteiger; Colleen M. Lau; Joseph C. Sun

Latent viral infections rely on a precise coordination of the immune response to control sporadic viral reactivation. CD8+ T cells play a crucial role in controlling viral latency by generating diverse memory responses in an epitope-specific manner. Among these distinct responses, conventional and inflationary memory responses have been described during herpesvirus infections. Using a newly generated TCR transgenic mouse strain, we investigated the transcriptomic and epigenetic remodeling of distinct epitope-specific CD8+ T cells during CMV infection across tissues at both population and single-cell levels. Our findings reveal that whereas the transcriptomic and epigenetic landscapes of conventional and inflationary memory responses diverge in the spleen and liver, these molecular programs converge in the salivary gland, a site of CMV persistence. Thus, we provide evidence that the dynamics of memory CD8+ T cell responses are distinct between tissues.