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

European journal of immunology: Volume 52, Issue 6, Page 895-906

CD8(+) memory T cells (T(M) ) 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(M) 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(M) 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(M) differentiation. Using peptide vaccination and viral infection, we studied CD8(+) T(M) differentiation in mice with an FRC-specific IFNAR deletion (FRC(ΔIFNAR) ). We show here that the differentiation of CD8(+) TCR-transgenic T cells into central memory cells (T(CM) ) is enhanced in peptide-vaccinated FRC(ΔIFNAR) mice. Conversely, vesicular stomatitis virus infection of FRC(ΔIFNAR) mice is associated with impaired T(CM) formation and the accumulation of vesicular stomatitis virus specific double-positive CD127(hi) KLRG-1(hi) effector memory T cells. In summary, we provide evidence for a context-dependent contribution of FRC-specific IFNAR signaling to CD8(+) T(M) differentiation.

DOI: 10.1002/eji.202149760