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

Abstract

CD8+ memory T cells (TM ) 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 TM 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+ TM 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+ TM differentiation. Using peptide vaccination and viral infection, we studied CD8+ TM differentiation in mice with an FRC-specific IFNAR deletion (FRCΔIFNAR ). We show here that the differentiation of CD8+ TCR-transgenic T cells into central memory cells (TCM ) is enhanced in peptide-vaccinated FRCΔIFNAR mice. Conversely, vesicular stomatitis virus infection of FRCΔIFNAR mice is associated with impaired TCM formation and the accumulation of vesicular stomatitis virus specific double-positive CD127hi KLRG-1hi effector memory T cells. In summary, we provide evidence for a context-dependent contribution of FRC-specific IFNAR signaling to CD8+ TM differentiation.

• Authors: Laura Knop, Julia Spanier, Pia-Katharina Larsen, Amelie Witte, Ute Bank, Ildiko R Dunay, Ulrich Kalinke, Thomas Schüler
• Journal: European journal of immunology (Eur J Immunol) Vol. 52 Issue 6 Pg. 895-906 (06 2022) ISSN: 1521-4141 [Electronic] Germany
• PMID: 35365883 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.

Chemical References

• Cancer Vaccines
• Vaccines, Subunit

Topics

• Animals
• CD8-Positive T-Lymphocytes
• Cancer Vaccines
• Fibroblasts
• Mice
• Mice, Inbred C57BL
• Vaccines, Subunit
• Vesicular Stomatitis (metabolism, pathology)