scholarly journals Rapid Effector Function in CD8+ Memory T Cells

1997 ◽  
Vol 186 (6) ◽  
pp. 859-865 ◽  
Author(s):  
Ajit Lalvani ◽  
Roger Brookes ◽  
Sophie Hambleton ◽  
Warwick J. Britton ◽  
Adrian V.S. Hill ◽  
...  
Keyword(s):  
T Cells ◽  
Influenza Virus ◽  
Cd8 T Cells ◽  
Ex Vivo ◽  
Influenza Virus Infection ◽  
Immunological Memory ◽  
Effector Function ◽  
Memory State ◽  
Memory Cd8 T Cells ◽  
Ifn Γ

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.

scholarly journals Resident memory CD8+T cells in the upper respiratory tract prevent pulmonary influenza virus infection

2017 ◽  
Vol 2 (12) ◽  
pp. eaam6970 ◽  
Author(s):  
Angela Pizzolla ◽  
Thi H. O. Nguyen ◽  
Jeffrey M. Smith ◽  
Andrew G. Brooks ◽  
Katherine Kedzierska ◽  
...  
Keyword(s):  
T Cells ◽  
Influenza Virus ◽  
Virus Infection ◽  
Respiratory Tract ◽  
Cd8 T Cells ◽  
Influenza Virus Infection ◽  
Upper Respiratory Tract ◽  
Memory Cd8 T Cells ◽  
Upper Respiratory

scholarly journals Osteopontin Modulates the Generation of Memory CD8+T Cells during Influenza Virus Infection

2011 ◽  
Vol 187 (11) ◽  
pp. 5671-5683 ◽  
Author(s):  
Junko Morimoto ◽  
Kayoko Sato ◽  
Yosuke Nakayama ◽  
Chiemi Kimura ◽  
Kiichi Kajino ◽  
...  
Keyword(s):  
T Cells ◽  
Influenza Virus ◽  
Virus Infection ◽  
Cd8 T Cells ◽  
Influenza Virus Infection ◽  
Memory Cd8 T Cells

scholarly journals In situ imaging reveals different responses by naïve and memory CD8 T cells to late antigen presentation by lymph node DC after influenza virus infection

2008 ◽  
Vol 38 (12) ◽  
pp. 3304-3315 ◽  
Author(s):  
Kamal M. Khanna ◽  
Carolina C. Aguila ◽  
Jason M. Redman ◽  
Jenny E. Suarez-Ramirez ◽  
Leo Lefrançois ◽  
...  
Keyword(s):  
T Cells ◽  
Influenza Virus ◽  
Lymph Node ◽  
Virus Infection ◽  
Antigen Presentation ◽  
Cd8 T Cells ◽  
Influenza Virus Infection ◽  
Memory Cd8 T Cells ◽  
Late Antigen

scholarly journals Checkpoint blockade accelerates a novel switch from an NKT-driven TNFα response toward a T cell driven IFN-γ response within the tumor microenvironment

2021 ◽  
Vol 9 (6) ◽  
pp. e002269
Author(s):  
Shota Aoyama ◽  
Ryosuke Nakagawa ◽  
Satoshi Nemoto ◽  
Patricio Perez-Villarroel ◽  
James J Mulé ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Tumor Growth ◽  
Ex Vivo ◽  
T Cell Response ◽  
Effector Function ◽  
Checkpoint Blockade ◽  
Necrosis Factor Alpha ◽  
Ifn Γ

BackgroundThe temporal response to checkpoint blockade (CB) is incompletely understood. Here, we profiled the tumor infiltrating lymphocyte (TIL) landscape in response to combination checkpoint blockade at two distinct timepoints of solid tumor growth.MethodsC57BL/6 mice bearing subcutaneous MC38 tumors were treated with anti-PD-1 and/or anti-CTLA-4 antibodies. At 11 or 21 days, TIL phenotype and effector function were analyzed in excised tumor digests using high parameter flow cytometry. The contributions of major TIL populations toward overall response were then assessed using ex vivo cytotoxicity and in vivo tumor growth assays.ResultsThe distribution and effector function among 37 distinct TIL populations shifted dramatically between early and late MC38 growth. At 11 days, the immune response was dominated by Tumor necrosis factor alpha (TNFα)-producing NKT, representing over half of all TIL. These were accompanied by modest frequencies of natural killer (NK), CD4+, or CD8+ T cells, producing low levels of IFN-γ. At 21 days, NKT populations were reduced to a combined 20% of TIL, giving way to increased NK, CD4+, and CD8+ T cells, with increased IFN-γ production. Treatment with CB accelerated this switch. At day 11, CB reduced NKT to less than 20% of all TIL, downregulated TNFα across NKT and CD4+ T cell populations, increased CD4+ and CD8+ TIL frequencies, and significantly upregulated IFN-γ production. Degranulation was largely associated with NK and NKT TIL. Blockade of H-2kb and/or CD1d during ex vivo cytotoxicity assays revealed NKT has limited direct cytotoxicity against parent MC38. However, forced CD1d overexpression in MC38 cells significantly diminished tumor growth, suggesting NKT TIL exerts indirect control over MC38 growth.ConclusionsDespite an indirect benefit of early NKT activity, CB accelerates a switch from TNFα, NKT-driven immune response toward an IFN-γ driven CD4+/CD8+ T cell response in MC38 tumors. These results uncover a novel NKT/T cell switch that may be a key feature of CB response in CD1d+ tumors.

Interleukin-15 Favors the Expansion of Central Memory CD8+ T Cells in Ex Vivo Generated, Antileukemia Human Cytotoxic T Lymphocyte Lines

2008 ◽  
Vol 31 (4) ◽  
pp. 385-393 ◽  
Author(s):  
Liane Daudt ◽  
Rita Maccario ◽  
Franco Locatelli ◽  
Ilaria Turin ◽  
Lucia Silla ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocyte ◽  
Cd8 T Cells ◽  
Cytotoxic T Lymphocyte ◽  
Ex Vivo ◽  
Central Memory ◽  
Memory Cd8 T Cells ◽  
Interleukin 15

scholarly journals Dendritic Cells Targeting Lactobacillus plantarum Strain NC8 with a Surface-Displayed Single-Chain Variable Fragment of CD11c Induce an Antigen-Specific Protective Cellular Immune Response

2019 ◽  
Vol 88 (2) ◽  
Author(s):  
Jing Liu ◽  
Guilian Yang ◽  
Haibin Huang ◽  
Chunwei Shi ◽  
Xing Gao ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Influenza Virus ◽  
Virus Infection ◽  
Lactobacillus Plantarum ◽  
Influenza Virus Infection ◽  
Cell Culture Supernatant ◽  
Single Chain ◽  
Ifn Γ

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.

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