scholarly journals Antibody-targeted vaccination to lung dendritic cells generates tissue-resident memory CD8 T cells that are highly protective against influenza virus infection

2015 ◽  
Vol 8 (5) ◽  
pp. 1060-1071 ◽  
Author(s):  
L M Wakim ◽  
J Smith ◽  
I Caminschi ◽  
M H Lahoud ◽  
J A Villadangos
2010 ◽  
Vol 207 (3) ◽  
pp. 521-534 ◽  
Author(s):  
Jodi McGill ◽  
Nico Van Rooijen ◽  
Kevin L. Legge

We have recently demonstrated that peripheral CD8 T cells require two separate activation hits to accumulate to high numbers in the lungs after influenza virus infection: a primary interaction with mature, antigen-bearing dendritic cells (DCs) in the lymph node, and a second, previously unrecognized interaction with MHC I–viral antigen–bearing pulmonary DCs in the lungs. We demonstrate that in the absence of lung-resident DC subsets, virus-specific CD8 T cells undergo significantly increased levels of apoptosis in the lungs; however, reconstitution with pulmonary plasmacytoid DCs and CD8α+ DCs promotes increased T cell survival and accumulation in the lungs. Further, our results show that the absence of DCs after influenza virus infection results in significantly reduced levels of IL-15 in the lungs and that pulmonary DC–mediated rescue of virus-specific CD8 T cell responses in the lungs requires trans-presentation of IL-15 via DC-expressed IL-15Rα. This study demonstrates a key, novel requirement for DC trans-presented IL-15 in promoting effector CD8 T cell survival in the respiratory tract after virus infection, and suggests that this trans-presentation could be an important target for the development of unique antiviral therapies and more effective vaccine strategies.


2017 ◽  
Vol 2 (12) ◽  
pp. eaam6970 ◽  
Author(s):  
Angela Pizzolla ◽  
Thi H. O. Nguyen ◽  
Jeffrey M. Smith ◽  
Andrew G. Brooks ◽  
Katherine Kedzierska ◽  
...  

2011 ◽  
Vol 187 (11) ◽  
pp. 5671-5683 ◽  
Author(s):  
Junko Morimoto ◽  
Kayoko Sato ◽  
Yosuke Nakayama ◽  
Chiemi Kimura ◽  
Kiichi Kajino ◽  
...  

2008 ◽  
Vol 38 (12) ◽  
pp. 3304-3315 ◽  
Author(s):  
Kamal M. Khanna ◽  
Carolina C. Aguila ◽  
Jason M. Redman ◽  
Jenny E. Suarez-Ramirez ◽  
Leo Lefrançois ◽  
...  

2019 ◽  
Vol 88 (2) ◽  
Author(s):  
Jing Liu ◽  
Guilian Yang ◽  
Haibin Huang ◽  
Chunwei Shi ◽  
Xing Gao ◽  
...  

ABSTRACT Influenza A virus (H1N1) is an acute, highly contagious respiratory virus. The use of lactic acid bacteria (LAB) to deliver mucosal vaccines against influenza virus infection is a research hot spot. In this study, two recombinant Lactobacillus plantarum strains expressing hemagglutinin (HA) alone or coexpressing aCD11c-HA to target HA protein to dendritic cells (DCs) by fusion to an anti-CD11c single-chain antibody (aCD11c) were constructed. The activation of bone marrow dendritic cells (BMDCs) by recombinant strains and the interaction of activated BMDCs and sorted CD4+ or CD8+ T cells were evaluated through flow cytometry in vitro, and cellular supernatants were assessed by using an enzyme-linked immunosorbent assay kit. The results demonstrated that, compared to the HA strain, the aCD11c-HA strain significantly increased the activation of BMDCs and increased the production of CD4+ gamma interferon-positive (IFN-γ+) T cells, CD8+ IFN-γ+ T cells, and IFN-γ in the cell culture supernatant in vitro. Consistent with these results, the aCD11c-HA strain clearly increased the activation and maturation of DCs, the HA-specific responses of CD4+ IFN-γ+ T cells, CD8+ IFN-γ+ T cells, and CD8+ CD107a+ T cells, and the proliferation of T cells in the spleen, finally increasing the levels of specific antibodies and neutralizing antibodies in mice. In addition, the protection of immunized mice was observed after viral infection, as evidenced by improved weight loss, survival, and lung pathology. The adoptive transfer of CD8+ T cells from the aCD11c-HA mice to NOD/Lt-SCID mice resulted in a certain level of protection after influenza virus infection, highlighting the efficacy of the aCD11c targeting strategy.


1997 ◽  
Vol 186 (6) ◽  
pp. 859-865 ◽  
Author(s):  
Ajit Lalvani ◽  
Roger Brookes ◽  
Sophie Hambleton ◽  
Warwick J. Britton ◽  
Adrian V.S. Hill ◽  
...  

The nature of the CD8+ T cells that underlie antiviral protective immunological memory in vivo is unclear. We have characterized peptide-specific CD8+ T lymphocytes directly ex vivo from peripheral blood in humans with past exposure to influenza virus, using single cell interferon γ (IFN-γ) release as a measure of effector function. In individuals in the memory state with respect to influenza virus infection, unrestimulated antigen-specific CD8+ T cells displayed IFN-γ release within 6 h of antigen contact, identifying a population of memory CD8+ T cells that exhibit effector function without needing to divide and differentiate over several days. We have quantified circulating CD8+ effector T cells specific for six different MHC class I–restricted influenza virus epitopes. Enumeration of these CD8+ T cells gives frequencies of peptide-specific T cells that correlate with, but are in general severalfold higher than, CTL precursor frequencies derived from limiting dilution analysis, indicating that this novel population of memory CD8+ T cells has hitherto been undetected by standard means. The phenotype of these cells, which persist at a low frequency long after recovery from an acute viral infection, suggests that they play a role in protective immunological memory.


2003 ◽  
Vol 198 (3) ◽  
pp. 399-410 ◽  
Author(s):  
Sherry R. Crowe ◽  
Stephen J. Turner ◽  
Shannon C. Miller ◽  
Alan D. Roberts ◽  
Rachel A. Rappolo ◽  
...  

The specificity of CD8+ T cell responses can vary dramatically between primary and secondary infections. For example, NP366–374/Db- and PA224–233/Db-specific CD8+ T cells respond in approximately equal numbers to a primary influenza virus infection in C57BL/6 mice, whereas NP366–374/Db-specific CD8+ T cells dominate the secondary response. To investigate the mechanisms underlying this changing pattern of immunodominance, we analyzed the role of antigen presentation in regulating the specificity of the T cell response. The data show that both dendritic and nondendritic cells are able to present the NP366–374/Db epitope, whereas only dendritic cells effectively present the PA224–233/Db epitope after influenza virus infection, both in vitro and in vivo. This difference in epitope expression favored the activation and expansion of NP366–374/Db-specific CD8+ memory T cells during secondary infection. The data also show that the immune response to influenza virus infection may involve T cells specific for epitopes, such as PA224–233/Db, that are poorly expressed at the site of infection. In this regard, vaccination with the PA224–233 peptide actually had a detrimental effect on the clearance of a subsequent influenza virus infection. Thus, differential antigen presentation impacts both the specificity of the T cell response and the efficacy of peptide-based vaccination strategies.


2016 ◽  
Vol 46 (12) ◽  
pp. 2778-2788 ◽  
Author(s):  
Li Jiang ◽  
Shuyu Yao ◽  
Su Huang ◽  
Jeffrey Wright ◽  
Thomas J. Braciale ◽  
...  

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