Cutting edge: polyinosinic:polycytidylic acid boosts the generation of memory CD8 T cells through melanoma differentiation-associated protein 5 expressed in stromal cells.

Abstract

Polyinosinic:polycytidylic acid (poly I:C), a synthetic analog of double-stranded viral RNA, serves as a potent adjuvant for vaccination against soluble proteins, pathogens, and tumors. Poly I:C is sensed by both TLR3 in the endosomes and melanoma differentiation-associated protein 5 (MDA5) in the cytoplasm. Although it is known that TLR3 is required for cross-priming of CD8 T cells specific for viral Ags, the role of MDA5 in inducing CD8 T cell responses is still unclear. In this study, we demonstrate that in mice lacking MDA5, the majority of CD8 T cells do not survive after primary immunization with poly I:C and Ag, impairing memory response to subsequent Ag challenge. Furthermore, bone marrow chimera experiments revealed that MDA5 expression in radiation-resistant stromal cells, but not in radiation-sensitive hematopoietic cells, is essential for establishing CD8 T cell memory. We conclude that MDA5 and TLR3 mediate substantially distinct yet complementary functions during poly I:C-mediated activation of Ag-specific CD8 T cell responses.

• Authors: Yaming Wang, Marina Cella, Susan Gilfillan, Marco Colonna
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 184 Issue 6 Pg. 2751-5 (Mar 15 2010) ISSN: 1550-6606 [Electronic] United States
• PMID: 20164430 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Epitopes, T-Lymphocyte
• TLR3 protein, mouse
• Toll-Like Receptor 3
• IFIH1 protein, human
• DEAD-box RNA Helicases
• Interferon-Induced Helicase, IFIH1
• Poly I-C

Topics

• Animals
• Bone Marrow Cells (immunology, metabolism, radiation effects)
• CD8-Positive T-Lymphocytes (immunology, metabolism, radiation effects)
• DEAD-box RNA Helicases (biosynthesis, deficiency, genetics, physiology)
• Epitopes, T-Lymphocyte (immunology)
• Gene Expression Regulation, Neoplastic (immunology, radiation effects)
• Hematopoietic Stem Cells (immunology, metabolism, radiation effects)
• Immunologic Memory
• Interferon-Induced Helicase, IFIH1
• Lymphocyte Activation (immunology, radiation effects)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Mice, Transgenic
• Poly I-C (pharmacology)
• Radiation Chimera
• Stromal Cells (immunology, metabolism, radiation effects)
• Toll-Like Receptor 3 (deficiency, genetics, physiology)