Production of IL-10 by CD4+ regulatory T cells during the resolution of infection promotes the maturation of memory CD8+ T cells

Brian J. Laidlaw; Weiguo Cui; Robert A. Amezquita; Simon M. Gray; Tianxia Guan; Yisi Lu; Yasushi Kobayashi; Richard A. Flavell; Steven H. Kleinstein; Joe Craft; Susan M. Kaech

doi:10.1038/ni.3224

Production of IL-10 by CD4⁺ regulatory T cells during the resolution of infection promotes the maturation of memory CD8⁺ T cells

Brian J. Laidlaw, Weiguo Cui, Robert A. Amezquita, Simon M. Gray, Tianxia Guan, Yisi Lu, Yasushi Kobayashi, Richard A. Flavell, Steven H. Kleinstein, Joe Craft, Susan M. Kaech

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159 Scopus citations

Abstract

Memory CD8⁺ T cells are critical for host defense upon reexposure to intracellular pathogens. We found that interleukin 10 (IL-10) derived from CD4⁺ regulatory T cells (T_reg cells) was necessary for the maturation of memory CD8⁺ T cells following acute infection with lymphocytic choriomeningitis virus (LCMV). T_reg cell-derived IL-10 was most important during the resolution phase, calming inflammation and the activation state of dendritic cells. Adoptive transfer of IL-10-sufficient T_reg cells during the resolution phase 'restored' the maturation of memory CD8⁺ T cells in IL-10-deficient mice. Our data indicate that T_reg cell-derived IL-10 is needed to insulate CD8⁺ T cells from inflammatory signals, and reveal that the resolution phase of infection is a critical period that influences the quality and function of developing memory CD8⁺ T cells.

Original language	English
Pages (from-to)	871-879
Number of pages	9
Journal	Nature immunology
Volume	16
Issue number	8
DOIs	https://doi.org/10.1038/ni.3224
State	Published - Jul 21 2015

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title = "Production of IL-10 by CD4+ regulatory T cells during the resolution of infection promotes the maturation of memory CD8+ T cells",

abstract = "Memory CD8+ T cells are critical for host defense upon reexposure to intracellular pathogens. We found that interleukin 10 (IL-10) derived from CD4+ regulatory T cells (Treg cells) was necessary for the maturation of memory CD8+ T cells following acute infection with lymphocytic choriomeningitis virus (LCMV). Treg cell-derived IL-10 was most important during the resolution phase, calming inflammation and the activation state of dendritic cells. Adoptive transfer of IL-10-sufficient Treg cells during the resolution phase 'restored' the maturation of memory CD8+ T cells in IL-10-deficient mice. Our data indicate that Treg cell-derived IL-10 is needed to insulate CD8+ T cells from inflammatory signals, and reveal that the resolution phase of infection is a critical period that influences the quality and function of developing memory CD8+ T cells.",

author = "Laidlaw, {Brian J.} and Weiguo Cui and Amezquita, {Robert A.} and Gray, {Simon M.} and Tianxia Guan and Yisi Lu and Yasushi Kobayashi and Flavell, {Richard A.} and Kleinstein, {Steven H.} and Joe Craft and Kaech, {Susan M.}",

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AU - Laidlaw, Brian J.

AU - Cui, Weiguo

AU - Amezquita, Robert A.

AU - Gray, Simon M.

AU - Guan, Tianxia

AU - Lu, Yisi

AU - Kobayashi, Yasushi

AU - Flavell, Richard A.

AU - Kleinstein, Steven H.

AU - Craft, Joe

AU - Kaech, Susan M.

PY - 2015/7/21

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AB - Memory CD8+ T cells are critical for host defense upon reexposure to intracellular pathogens. We found that interleukin 10 (IL-10) derived from CD4+ regulatory T cells (Treg cells) was necessary for the maturation of memory CD8+ T cells following acute infection with lymphocytic choriomeningitis virus (LCMV). Treg cell-derived IL-10 was most important during the resolution phase, calming inflammation and the activation state of dendritic cells. Adoptive transfer of IL-10-sufficient Treg cells during the resolution phase 'restored' the maturation of memory CD8+ T cells in IL-10-deficient mice. Our data indicate that Treg cell-derived IL-10 is needed to insulate CD8+ T cells from inflammatory signals, and reveal that the resolution phase of infection is a critical period that influences the quality and function of developing memory CD8+ T cells.

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Production of IL-10 by CD4⁺ regulatory T cells during the resolution of infection promotes the maturation of memory CD8⁺ T cells

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