IFNAR signaling in fibroblastic reticular cells can modulate CD8 memory fate decision.

CD8 memory T cells (T ) are crucial for long-term protection from infections and cancer. Multiple cell types and cytokines are involved in the regulation of CD8 T cell responses and subsequent T formation. Besides their direct antiviral effects, type I interferons (IFN-I) modulate CD8 T cell immunity via their action on several immune cell subsets. However, it is largely unclear how nonimmune cells are involved in this multicellular network modulating CD8 T formation. Fibroblastic reticular cells (FRCs) form the 3D scaffold of secondary lymphoid organs, express the IFN-I receptor (IFNAR), and modulate adaptive immune responses. However, it is unclear whether and how early IFNAR signals in lymph node (LN) FRCs affect CD8 T differentiation. Using peptide vaccination and viral infection, we studied CD8 T differentiation in mice with an FRC-specific IFNAR deletion (FRC ). We show here that the differentiation of CD8 TCR-transgenic T cells into central memory cells (T ) is enhanced in peptide-vaccinated FRC mice. Conversely, vesicular stomatitis virus infection of FRC mice is associated with impaired T formation and the accumulation of vesicular stomatitis virus specific double-positive CD127 KLRG-1 effector memory T cells. In summary, we provide evidence for a context-dependent contribution of FRC-specific IFNAR signaling to CD8 T differentiation.