Programming Multifaceted Pulmonary T Cell Immunity by Combination Adjuvants.
Programming Multifaceted Pulmonary T Cell Immunity by Combination Adjuvants.
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DOI：
10.1016/j.xcrm.2020.100095
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发表时间：
2020-09-22
期刊：
影响因子：
--
通讯作者：
Suresh M
中科院分区：
文献类型：
--
作者：
Marinaik CB;Kingstad-Bakke B;Lee W;Hatta M;Sonsalla M;Larsen A;Neldner B;Gasper DJ;Kedl RM;Kawaoka Y;Suresh M
Induction of protective mucosal T cell memory remains a formidable challenge to vaccinologists. Using a combination adjuvant strategy that elicits potent CD8 and CD4 T cell responses, we define the tenets of vaccine-induced pulmonary T cell immunity. An acrylic-acid-based adjuvant (ADJ), in combination with Toll-like receptor (TLR) agonists glucopyranosyl lipid adjuvant (GLA) or CpG, promotes mucosal imprinting but engages distinct transcription programs to drive different degrees of terminal differentiation and disparate polarization of TH1/TC1/TH17/TC17 effector/memory T cells. Combination of ADJ with GLA, but not CpG, dampens T cell receptor (TCR) signaling, mitigates terminal differentiation of effectors, and enhances the development of CD4 and CD8 TRM cells that protect against H1N1 and H5N1 influenza viruses. Mechanistically, vaccine-elicited CD4 T cells play a vital role in optimal programming of CD8 TRM and viral control. Taken together, these findings provide further insights into vaccine-induced multifaceted mucosal T cell immunity with implications in the development of vaccines against respiratorypathogens, including influenza virus and SARS-CoV-2. Combination adjuvants stimulate potent TRM cell immunity in the respiratory tract Differentiation and functional programming depend on adjuvant and TCR signaling Vaccine-induced T cell immunity to influenza requires CD4 and CD8 T cells CD4 T cells regulate optimal positioning and programming of CD8 TRM in lungs Marinaik et al. report that carbomer and TLR-based combination adjuvants elicit airway- and lung-resident memory and confer heterosubtypic immunity to influenza virus. Further, they show that combination adjuvants stimulate varying levels of TCR signaling and cytokines in lungs and drive disparate patterns of effector/memory differentiation, mucosal imprinting, and functional polarization.
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DOI：
10.4049/jimmunol.1200571
发表时间：
2013-01-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Hamada H;Bassity E;Flies A;Strutt TM;Garcia-Hernandez Mde L;McKinstry KK;Zou T;Swain SL;Dutton RW
通讯作者：
Dutton RW
DOI：
10.4049/jimmunol.0801814
发表时间：
2009-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Hamada H;Garcia-Hernandez Mde L;Reome JB;Misra SK;Strutt TM;McKinstry KK;Cooper AM;Swain SL;Dutton RW
通讯作者：
Dutton RW
影响因子：
30.5
作者：
Iwata A;Durai V;Tussiwand R;Briseño CG;Wu X;Grajales-Reyes GE;Egawa T;Murphy TL;Murphy KM
通讯作者：
Murphy KM
影响因子：
6.7
作者：
Gasper DJ;Neldner B;Plisch EH;Rustom H;Carrow E;Imai H;Kawaoka Y;Suresh M
通讯作者：
Suresh M
影响因子：
32.4
作者：
Gerlach, Carmen;Moseman, E. Ashley;Loughhead, Scott M.;Alvarez, David;Zwijnenburg, Anthonie J.;Waanders, Lisette;Garg, Rohit;de la Torre, Juan C.;von Andrian, Ulrich H.
通讯作者：
von Andrian, Ulrich H.