학술논문

Migratory DCs activate TGF-β to precondition naïve CD8+ T cells for tissue-resident memory fate
Document Type
article
Source
Science. 366(6462)
Subject
Vaccine Related
Prevention
Immunization
1.1 Normal biological development and functioning
Underpinning research
Inflammatory and immune system
Animals
CD8-Positive T-Lymphocytes
Cell Movement
Dendritic Cells
Epidermis
Immunologic Memory
Integrin alphaV
Lymph Nodes
Mice
Mice
Inbred C57BL
Mice
Transgenic
Skin
Transforming Growth Factor beta
General Science & Technology
Language
Abstract
Epithelial resident memory T (eTRM) cells serve as sentinels in barrier tissues to guard against previously encountered pathogens. How eTRM cells are generated has important implications for efforts to elicit their formation through vaccination or prevent it in autoimmune disease. Here, we show that during immune homeostasis, the cytokine transforming growth factor β (TGF-β) epigenetically conditions resting naïve CD8+ T cells and prepares them for the formation of eTRM cells in a mouse model of skin vaccination. Naïve T cell conditioning occurs in lymph nodes (LNs), but not in the spleen, through major histocompatibility complex class I-dependent interactions with peripheral tissue-derived migratory dendritic cells (DCs) and depends on DC expression of TGF-β-activating αV integrins. Thus, the preimmune T cell repertoire is actively conditioned for a specialized memory differentiation fate through signals restricted to LNs.