@article{3616c3552ada4def96839619ca8df0b9,
title = "Memory-phenotype CD4+ T cells spontaneously generated under steady-state conditions exert innate TH1-like effector function",
abstract = "Conventional CD4+ T cells are composed of na{\"i}ve, pathogen-specific memory, and pathogen-independent memory-phenotype (MP) cells under steady state. Na{\"i}ve and pathogen-specific memory cells play key roles in adaptive immunity, whereas the homeostatic mechanisms regulating the generation of MP cells and their biological functions are unclear. We show that MP cells are autonomously generated from peripheral na{\"i}ve cells in the absence of infectious stimulation in a T cell receptor (TCR)– and CD28-dependent manner. We further demonstrate that MP cells contain a T-bethi subpopulation that is continuously generated by environmental interleukin-12 (IL-12) and rapidly produces interferon- (IFN-) in response to IL-12 in the absence of pathogen recognition. These cells can provide nonspecific host resistance against Toxoplasma gondii infection while enhancing the adaptive CD4+ T cell responses. Together, these findings reveal that MP cells are continuously generated from na{\"i}ve precursors and have a previously undescribed innate immune function by which they produce an early, T helper cell type 1 (TH1)–like protective response against pathogens.",
author = "Takeshi Kawabe and Dragana Jankovic and Shuko Kawabe and Yuefeng Huang and Lee, {Ping Hsien} and Hidehiro Yamane and Jinfang Zhu and Alan Sher and Germain, {Ronald N.} and Paul, {William E.}",
note = "Funding Information: We thank Y. Belkaid (NIAID, NIH) for GF mice; K. S. Hathcock (National Cancer Institute, NIH) and R. J. Hodes (National Institute on Aging, NIH) for Rag2-GFP mice; N. Ishii (Tohoku University, Japan) for research support; T. G. Myers (NIAID, NIH) for RNA-seq; E. M. Shevach (NIAID, NIH) for thoughtful discussions; T. Takahashi (Central Institute for Experimental Animals, Japan) for experiments using neonatal animals; NIH Tetramer Core Facility for tetramers; D. L. Costa and S. Sakai for M. bovis BCG; J. Hu-Li, X. Chen, S. Hieny, S. D. Oland, and L. Mittereder for technical assistance; and K. L. Holmes, C. C. Henry, and K. Weng for cell sorting. We deeply regret the loss of W.E.P. who passed away on 18 September 2015. This work was supported by the Intramural Research Program of the NIAID, NIH. T.K. was supported by a grant from Japan Society for the Promotion of Science. Publisher Copyright: Copyright {\textcopyright} 2017 The Authors.",
year = "2017",
doi = "10.1126/sciimmunol.aam9304",
language = "English",
volume = "2",
journal = "Science immunology",
issn = "2470-9468",
publisher = "American Association for the Advancement of Science",
number = "12",
}