RRC ID 50500
Author Herndler-Brandstetter D, Ishigame H, Shinnakasu R, Plajer V, Stecher C, Zhao J, Lietzenmayer M, Kroehling L, Takumi A, Kometani K, Inoue T, Kluger Y, Kaech SM, Kurosaki T, Okada T, Flavell RA.
Title KLRG1+ Effector CD8+ T Cells Lose KLRG1, Differentiate into All Memory T Cell Lineages, and Convey Enhanced Protective Immunity.
Journal Immunity
Abstract Protective immunity against pathogens depends on the efficient generation of functionally diverse effector and memory T lymphocytes. However, whether plasticity during effector-to-memory CD8+ T cell differentiation affects memory lineage specification and functional versatility remains unclear. Using genetic fate mapping analysis of highly cytotoxic KLRG1+ effector CD8+ T cells, we demonstrated that KLRG1+ cells receiving intermediate amounts of activating and inflammatory signals downregulated KLRG1 during the contraction phase in a Bach2-dependent manner and differentiated into all memory T cell linages, including CX3CR1int peripheral memory cells and tissue-resident memory cells. "ExKLRG1" memory cells retained high cytotoxic and proliferative capacity distinct from other populations, which contributed to effective anti-influenza and anti-tumor immunity. Our work demonstrates that developmental plasticity of KLRG1+ effector CD8+ T cells is important in promoting functionally versatile memory cells and long-term protective immunity.
Volume 48(4)
Pages 716-729.e8
Published 2018-4-17
DOI 10.1016/j.immuni.2018.03.015
PII S1074-7613(18)30091-8
PMID 29625895
PMC PMC6465538
MeSH Animals Basic-Leucine Zipper Transcription Factors / genetics CD8-Positive T-Lymphocytes / cytology* CD8-Positive T-Lymphocytes / immunology* Cell Differentiation / immunology Cell Line, Tumor Cell Lineage / immunology Immunologic Memory / immunology* Influenza A virus / immunology Interleukin-12 Subunit p35 / immunology Lectins, C-Type Listeria monocytogenes / immunology Lymphocyte Activation / immunology* Melanoma, Experimental Mice Mice, Inbred C57BL Mice, Knockout Receptors, Immunologic / genetics Receptors, Immunologic / metabolism* Vesicular stomatitis Indiana virus / immunology
IF 22.553
Times Cited 63
Mice RBRC01834