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Effector CD4 T-cell transition to memory requires late cognate interactions that induce autocrine IL-2.

ABSTRACT: It is unclear how CD4 T-cell memory formation is regulated following pathogen challenge, and when critical mechanisms act to determine effector T-cell fate. Here, we report that following influenza infection most effectors require signals from major histocompatibility complex class II molecules and CD70 during a late window well after initial priming to become memory. During this timeframe, effector cells must produce IL-2 or be exposed to high levels of paracrine or exogenously added IL-2 to survive an otherwise rapid default contraction phase. Late IL-2 promotes survival through acute downregulation of apoptotic pathways in effector T cells and by permanently upregulating their IL-7 receptor expression, enabling IL-7 to sustain them as memory T cells. This new paradigm defines a late checkpoint during the effector phase at which cognate interactions direct CD4 T-cell memory generation.

SUBMITTER: McKinstry KK

PROVIDER: S-EPMC4223689 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Effector CD4 T-cell transition to memory requires late cognate interactions that induce autocrine IL-2.

McKinstry K Kai KK Strutt Tara M TM Bautista Bianca B Zhang Wenliang W Kuang Yi Y Cooper Andrea M AM Swain Susan L SL

Nature communications 20141105

It is unclear how CD4 T-cell memory formation is regulated following pathogen challenge, and when critical mechanisms act to determine effector T-cell fate. Here, we report that following influenza infection most effectors require signals from major histocompatibility complex class II molecules and CD70 during a late window well after initial priming to become memory. During this timeframe, effector cells must produce IL-2 or be exposed to high levels of paracrine or exogenously added IL-2 to su ...[more]

PMID: 25369785

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