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Early commitment in the steady state programs antigen specific CD4+ T cells for subsequent effector differentiation [ChIP]

ABSTRACT: Epigenetic profile of CD4 positive naïve and dendritic cell-activated T cells

ORGANISM(S): Mus musculus

PROVIDER: GSE141723 | GEO | 2020/11/24

REPOSITORIES: GEO

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Early commitment in the steady state programs antigen specific CD4+ T cells for subsequent effector differentiation

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Early commitment in the steady state programs antigen specific CD4+ T cells for subsequent effector differentiation

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Memory-phenotype CD4+ T cells spontaneously generated under steady-state conditions exert innate TH1-like effector function.

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Project description:Although memory CD4 T cells are critical for effective immunity to pathogens, the mechanisms underlying their generation are still poorly defined. We find that following murine influenza infection, most effector CD4 T cells undergo apoptosis unless they encounter cognate Ag at a defined stage near the peak of effector generation. Ag recognition at this memory checkpoint blocks default apoptosis and programs their transition to long-lived memory. Strikingly, we find that viral infection is not required, because memory formation can be restored by the addition of short-lived, Ag-pulsed APC at this checkpoint. The resulting memory CD4 T cells express an enhanced memory phenotype, have increased cytokine production, and provide protection against lethal influenza infection. Finally, we find that memory CD4 T cell formation following cold-adapted influenza vaccination is boosted when Ag is administered during this checkpoint. These findings imply that persistence of viral Ag presentation into the effector phase is the key factor that determines the efficiency of memory generation. We also suggest that administering Ag at this checkpoint may improve vaccine efficacy.

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