Intrinsic IL-2 production by effector CD8 T cells affects IL-2 signaling and promotes fate decisions, stemness, and protection

Here, we show that the capacity to manufacture IL-2 identifies constituents of the expanded CD8 T cell effector pool that display stem-like features, preferentially survive, rapidly attain memory traits, resist exhaustion, and control chronic viral challenges. The cell-intrinsic synthesis of IL-2 by...

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Veröffentlicht in:Science immunology Jg. 7; H. 68; S. eabl6322
Hauptverfasser: Kahan, Shannon M, Bakshi, Rakesh K, Ingram, Jennifer T, Hendrickson, R Curtis, Lefkowitz, Elliot J, Crossman, David K, Harrington, Laurie E, Weaver, Casey T, Zajac, Allan J
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 11.02.2022
Schlagworte:
Animals
CD8-Positive T-Lymphocytes - immunology
Interleukin-2 - biosynthesis
Interleukin-2 - immunology
Mice
Mice, Congenic
Mice, Transgenic
Signal Transduction - immunology
STAT5 Transcription Factor - immunology
ISSN:2470-9468, 2470-9468
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Zusammenfassung:Here, we show that the capacity to manufacture IL-2 identifies constituents of the expanded CD8 T cell effector pool that display stem-like features, preferentially survive, rapidly attain memory traits, resist exhaustion, and control chronic viral challenges. The cell-intrinsic synthesis of IL-2 by CD8 T cells attenuates the ability to receive IL-2-dependent STAT5 signals, thereby limiting terminal effector formation, endowing the IL-2-producing effector subset with superior protective powers. In contrast, the non-IL-2-producing effector cells respond to IL-2 signals and gain effector traits at the expense of memory formation. Despite having distinct properties during the effector phase, IL-2-producing and nonproducing CD8 T cells appear to converge transcriptionally as memory matures to form populations with equal recall abilities. Therefore, the potential to produce IL-2 during the effector, but not memory stage, is a consequential feature that dictates the protective capabilities of the response.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:2470-9468
2470-9468
DOI:10.1126/sciimmunol.abl6322