Abstract：
:Viral persistence specifically inhibits CD4 Th1 responses and promotes Tfh immunity, but the mechanisms that suppress Th1 cells and the disease consequences of their loss are unclear. Here, we demonstrate that the loss of CD4 Th1 cells specifically leads to progressive CD8 T cell decline and dysfunction during viral persistence. Therapeutically reconstituting CD4 Th1 cells restored CD4 T cell polyfunctionality, enhanced antiviral CD8 T cell numbers and function, and enabled viral control. Mechanistically, combined interaction of PD-L1 and IL-10 by suppressive dendritic cell subsets inhibited new CD4 Th1 cells in both acute and persistent virus infection, demonstrating an unrecognized suppressive function for PD-L1 in virus infection. Thus, the loss of CD4 Th1 cells is a key event leading to progressive CD8 T cell demise during viral persistence with important implications for restoring antiviral CD8 T cell immunity to control persistent viral infection.
journal_name
Cell Repjournal_title
Cell reportsauthors
Snell LM,Osokine I,Yamada DH,De la Fuente JR,Elsaesser HJ,Brooks DGdoi
10.1016/j.celrep.2016.08.065subject
Has Abstractpub_date
2016-09-20 00:00:00pages
3286-3296issue
12issn
2211-1247pii
S2211-1247(16)31146-9journal_volume
16pub_type
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