Splenic fibroblastic reticular cells orchestrate dendritic cell maturation and facilitate CD8⁺ T cell priming and protective memory.

Abstract

Fibroblastic reticular cells (FRCs) are specialized fibroblasts that construct secondary lymphoid organs where they provide crucial signals for immune cell homeostasis and migration. While splenic FRCs are thought to support antiviral T cell responses, their role remains unclear. Here, we found that ablation of splenic FRCs impaired virus-specific CD8⁺ T cell responses during lymphocytic choriomeningitis virus (LCMV) infection. Immunofluorescence imaging revealed that FRCs promote CD8⁺ T cell clustering with type 1 conventional dendritic cells (cDC1) in the T cell zone before migration to the infected marginal zone. Without FRCs, T cells instead clustered with cDC1 and virus-infected cells in the marginal zone, leading to suboptimal priming. Mechanistically, FRCs coordinated early viral replication and the inflammatory milieu for optimal DC activation, and an intact FRC network was crucial for generating effector T cells and maintaining protective memory T cells. Thus, splenic FRCs provide essential lymphoid niches for antiviral T cell responses.