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Early commitment in the steady state programs antigen specific CD4+ T cells for subsequent effector differentiation [12hRNA]

ABSTRACT: RNA expression in CD4 positive naïve and dendritic cell-activated T cells

ORGANISM(S): Mus musculus

PROVIDER: GSE141722 | 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

Project description:RNA expression in CD4 positive naïve and dendritic cell-activated T cells

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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

Project description: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 [12hRNA]

Project description:Early commitment in the steady state programs antigen specific CD4+ T cells for subsequent effector differentiation [12hRNA]

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

Project description:Conventional CD4+ T cells are composed of naïve, pathogen-specific memory, and pathogen-independent memory-phenotype (MP) cells under steady state. Naïve and pathogen-specific memory cells play key roles in adaptive immunity, whereas the homeostatic mechanisms regulating the generation of MP cells and their biological functions are unclear. We show that MP cells are autonomously generated from peripheral naïve cells in the absence of infectious stimulation in a T cell receptor (TCR)- and CD28-dependent manner. We further demonstrate that MP cells contain a T-bethi subpopulation that is continuously generated by environmental interleukin-12 (IL-12) and rapidly produces interferon-γ (IFN-γ) in response to IL-12 in the absence of pathogen recognition. These cells can provide nonspecific host resistance against Toxoplasma gondii infection while enhancing the adaptive CD4+ T cell responses. Together, these findings reveal that MP cells are continuously generated from naïve precursors and have a previously undescribed innate immune function by which they produce an early, T helper cell type 1 (TH1)-like protective response against pathogens.

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Short-Lived Antigen Recognition but Not Viral Infection at a Defined Checkpoint Programs Effector CD4 T Cells To Become Protective Memory.

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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A Two-Step Process of Effector Programming Governs CD4<sup>+</sup> T Cell Fate Determination Induced by Antigenic Activation in the Steady State.

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