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

First Author  Wang Y Year  2010
Journal  J Immunol Volume  184
Issue  6 Pages  2751-5
PubMed ID  20164430 Mgi Jnum  J:160108
Mgi Id  MGI:4453425 Doi  10.4049/jimmunol.0903201
Citation  Wang Y, et al. (2010) Cutting edge: polyinosinic:polycytidylic acid boosts the generation of memory CD8 T cells through melanoma differentiation-associated protein 5 expressed in stromal cells. J Immunol 184(6):2751-5
abstractText  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.
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