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

• Published in: Science immunology Vol. 7; no. 68; p. eabl6322
• Main Authors: 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
• Language: English
• Published: United States 11.02.2022
• Subjects: 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
• DOI: 10.1126/sciimmunol.abl6322

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.