Overcoming CD4 Th1 Cell Fate Restrictions to Sustain Antiviral CD8 T Cells and Control Persistent Virus Infection
Autor: | Justin Rafael de la Fuente, David G. Brooks, Laura M. Snell, Douglas H. Yamada, Ivan Osokine, Heidi Elsaesser |
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Jazyk: | angličtina |
Předmět: |
0301 basic medicine
Transgene Mice Transgenic Disease CD8-Positive T-Lymphocytes Lymphocytic Choriomeningitis Cell fate determination Biology Article B7-H1 Antigen General Biochemistry Genetics and Molecular Biology Virus Mice 03 medical and health sciences 0302 clinical medicine Immunity Animals Cytotoxic T cell lcsh:QH301-705.5 Cell Differentiation Dendritic cell Th1 Cells Virology Interleukin-10 Mice Inbred C57BL 030104 developmental biology lcsh:Biology (General) Immunology CD8 030215 immunology |
Zdroj: | Cell Reports, Vol 16, Iss 12, Pp 3286-3296 (2016) |
ISSN: | 2211-1247 |
DOI: | 10.1016/j.celrep.2016.08.065 |
Popis: | SummaryViral 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. |
Databáze: | OpenAIRE |
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