Local Inflammatory Cues Regulate Differentiation and Persistence of CD8+ Tissue-Resident Memory T Cells

Publication date: 4 April 2017
Source:Cell Reports, Volume 19, Issue 1
Author(s): Tessa Bergsbaken, Michael J. Bevan, Pamela J. Fink
Many pathogens initiate infection at mucosal surfaces, and tissue-resident memory T (Trm) cells play an important role in protective immunity, yet the tissue-specific signals that regulate Trm differentiation are poorly defined. During Yersinia infection, CD8⁺ T cell recruitment to areas of inflammation within the intestine is required for differentiation of the CD103⁻CD69⁺ Trm subset. Intestinal proinflammatory microenvironments have elevated interferon (IFN)-β and interleukin-12 (IL-12), which regulated Trm markers, including CD103. Type I interferon-receptor- or IL-12-receptor-deficient T cells functioned similarly to wild-type (WT) cells during infection; however, the inability of T cells to respond to inflammation resulted in defective differentiation of CD103⁻CD69⁺ Trm cells and reduced Trm persistence. Intestinal macrophages were the main producers of IFN-β and IL-12 during infection, and deletion of CCR2⁺ IL-12-producing cells reduced the size of the CD103⁻ Trm population. These data indicate that intestinal inflammation drives phenotypic diversity and abundance of Trm cells for optimal tissue-specific immunity.

Graphical abstract

Teaser

Tissue-specific signals that regulate the differentiation and maintenance of tissue resident memory T cells (Trm) remain poorly defined. Bergsbaken et al. identify IL-12 and type I interferon produced during local infection as regulators of Trm differentiation and persistence within the intestinal tissue.


http://ift.tt/2nKbE2C