CD4+ T cell help creates memory CD8+ T cells with innate and help-independent recall capacities

被引:104
作者
Ahrends, Tomasz [1 ,4 ]
Busselaar, Julia [1 ,5 ]
Severson, Tesa M. [2 ]
Babala, Nikolina [1 ]
de Vries, Evert [1 ,5 ]
Bovens, Astrid [1 ]
Wessels, Lodewyk [2 ]
van Leeuwen, Fred [3 ]
Borst, Jannie [1 ,5 ]
机构
[1] Netherlands Canc Inst Antoni van Leeuwenhoek, Div Tumor Biol & Immunol, NL-1066 CX Amsterdam, Netherlands
[2] Netherlands Canc Inst Antoni van Leeuwenhoek, Div Mol Carcinogenesis, Oncode Inst, NL-1066 CX Amsterdam, Netherlands
[3] Netherlands Canc Inst Antoni van Leeuwenhoek, Div Gene Regulat, NL-1066 CX Amsterdam, Netherlands
[4] Rockefeller Univ, Lab Mucosal Immunol, 1230 York Ave, New York, NY 10021 USA
[5] Leiden Univ, Dept Immunohematol & Blood Transfus, Med Ctr, Leiden, Netherlands
关键词
EFFECTOR; ACTIVATION; EXHAUSTION; EXPRESSION; VACCINES; SUBSETS; ANTIGEN; CANCER; NAIVE;
D O I
10.1038/s41467-019-13438-1
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
CD4(+) T cell help is required for the generation of CD8(+) cytotoxic T lymphocyte (CTL) memory. Here, we use genome-wide analyses to show how CD4(+) T cell help delivered during priming promotes memory differentiation of CTLs. Help signals enhance IL-15-dependent maintenance of central memory T (T-CM) cells. More importantly, help signals regulate the size and function of the effector memory T (T-EM ) cell pool. Helped T-EM cells produce Granzyme B and IFN gamma upon antigen-independent, innate-like recall by IL-12 and IL-18. In addition, helped memory CTLs express the effector program characteristic of helped primary CTLs upon recall with MHC class I-restricted antigens, likely due to epigenetic imprinting and sustained mRNA expression of effector genes. Our data thus indicate that during priming, CD4(+) T cell help optimizes CTL memory by creating T-EM cells with innate and helpindependent antigen-specific recall capacities.
引用
收藏
页数:13
相关论文
共 52 条
[1]   CD4+ T Cell Help Confers a Cytotoxic T Cell Effector Program Including Coinhibitory Receptor Downregulation and Increased Tissue Invasiveness [J].
Ahrends, Tomasz ;
Spanjaard, Aldo ;
Pilzecker, Bas ;
Babala, Nikolina ;
Bovens, Astrid ;
Xiao, Yanling ;
Jacobs, Heinz ;
Borst, Jannie .
IMMUNITY, 2017, 47 (05) :848-+
[2]   CD27 Agonism Plus PD-1 Blockade Recapitulates CD4+ T-cell Help in Therapeutic Anticancer Vaccination [J].
Ahrends, Tomasz ;
Babala, Nikolina ;
Xiao, Yanling ;
Yagita, Hideo ;
van Eenennaam, Hans ;
Borst, Jannie .
CANCER RESEARCH, 2016, 76 (10) :2921-2931
[3]   TOX reinforces the phenotype and longevity of exhausted T cells in chronic viral infection [J].
Alfei, Francesca ;
Kanev, Kristiyan ;
Hofmann, Maike ;
Wu, Ming ;
Ghoneim, Hazem E. ;
Roelli, Patrick ;
Utzschneider, Daniel T. ;
von Hoesslin, Madlaina ;
Cullen, Jolie G. ;
Fan, Yiping ;
Eisenberg, Vasyl ;
Wohlleber, Dirk ;
Steiger, Katja ;
Merkler, Doron ;
Delorenzi, Mauro ;
Knolle, Percy A. ;
Cohen, Cyrille J. ;
Thimme, Robert ;
Youngblood, Benjamin ;
Zehn, Dietmar .
NATURE, 2019, 571 (7764) :265-+
[4]   Genome-wide Analysis of Histone Methylation Reveals Chromatin State-Based Regulation of Gene Transcription and Function of Memory CD8+ T Cells [J].
Araki, Yasuto ;
Wang, Zhibin ;
Zang, Chongzhi ;
Wood, William H., III ;
Schones, Dustin ;
Cui, Kairong ;
Roh, Tae-Young ;
Lhotsky, Brad ;
Wersto, Robert P. ;
Peng, Weiqun ;
Becker, Kevin G. ;
Zhao, Keji ;
Weng, Nan-ping .
IMMUNITY, 2009, 30 (06) :912-925
[5]   Subcellular Localization of Antigen in Keratinocytes Dictates Delivery of CD4+ T-cell Help for the CTL Response upon Therapeutic DNA Vaccination into the Skin [J].
Babala, Nikolina ;
Bovens, Astrid ;
de Vries, Evert ;
Iglesias-Guimarais, Victoria ;
Ahrends, Tomasz ;
Krummel, Matthew F. ;
Borst, Jannie ;
Bins, Adriaan D. .
CANCER IMMUNOLOGY RESEARCH, 2018, 6 (07) :835-847
[6]   CD4+ T-cell help amplifies innate signals for primary CD8+ T-cell immunity [J].
Bedoui, Sammy ;
Heath, William R. ;
Mueller, Scott N. .
IMMUNOLOGICAL REVIEWS, 2016, 272 (01) :52-64
[7]   Helping the CD8+ T-cell response [J].
Bevan, MJ .
NATURE REVIEWS IMMUNOLOGY, 2004, 4 (08) :595-602
[8]   CD4+ T cell help in cancer immunology and immunotherapy [J].
Borst, Jannie ;
Ahrends, Tomasz ;
Babala, Nikolina ;
Melief, Cornelis J. M. ;
Kastenmueller, Wolfgang .
NATURE REVIEWS IMMUNOLOGY, 2018, 18 (10) :635-647
[9]   CD8+ T Cells Orchestrate pDC-XCR1+ Dendritic Cell Spatial and Functional Cooperativity to Optimize Priming [J].
Brewitz, Anna ;
Eickhoff, Sarah ;
Daehling, Sabrina ;
Quast, Thomas ;
Bedoui, Sammy ;
Kroczek, Richard A. ;
Kurts, Christian ;
Garbi, Natalio ;
Barchet, Winfried ;
Iannacone, Matteo ;
Klauschen, Frederick ;
Kolanus, Waldemar ;
Kaisho, Tsuneyasu ;
Colonna, Marco ;
Germain, Ronald N. ;
Kastenmueller, Wolfgang .
IMMUNITY, 2017, 46 (02) :205-219
[10]   An ultra-low-input native ChIP-seq protocol for genome-wide profiling of rare cell populations [J].
Brind'Amour, Julie ;
Liu, Sheng ;
Hudson, Matthew ;
Chen, Carol ;
Karimi, Mohammad M. ;
Lorincz, Matthew C. .
NATURE COMMUNICATIONS, 2015, 6