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Effector CD4 T cell transition to memory requires late cognate interactions that induce autocrine IL-2
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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4223689/ https://www.ncbi.nlm.nih.gov/pubmed/25369785 http://dx.doi.org/10.1038/ncomms6377 |
Sumario: | 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 down regulation 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. |
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