In situ imaging studies reveal different responses by naïve and memory CD8 T cells to late antigen presentation by lymph node DC after influenza infection

Non-hematopoietic lymph node stromal cells shape immunity by inducing MHC-I-dependent deletion of self-reactive CD8+ T cells and MHC-II-dependent anergy of CD4+ T cells. In this study, we show that MHC-II expression on lymph node stromal cells is additionally required for homeostatic maintenance of regulatory T cells (Tregs) and maintenance of immune quiescence. In the absence of MHC-II expression in lymph node transplants, i.e. on lymph node stromal cells, CD4+ as well as CD8+ T cells became activated, ultimately resulting in transplant rejection. MHC-II self-antigen presentation by lymph node stromal cells allowed the non-proliferative maintenance of antigen-specific Tregs and constrained antigen-specific immunity. Altogether, our results reveal a novel mechanism by which lymph node stromal cells regulate peripheral immunity.

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OVX836 Heptameric Nucleoprotein Vaccine Generates Lung Tissue-Resident Memory CD8+ T-Cells for Cross-Protection Against Influenza

Frontiers in Immunology ◽

10.3389/fimmu.2021.678483 ◽

2021 ◽

Vol 12 ◽

Author(s):

Judith Del Campo ◽

Julien Bouley ◽

Marion Chevandier ◽

Carine Rousset ◽

Marjorie Haller ◽

...

Keyword(s):

T Cells ◽

Recombinant Protein ◽

Dna Sequence ◽

Cd8 T Cells ◽

Influenza A ◽

Influenza Infection ◽

Influenza Viruses ◽

Protein Vaccine ◽

Memory Cd8 T Cells

Tissue-resident memory (TRM) CD8+ T-cells play a crucial role in the protection against influenza infection but remain difficult to elicit using recombinant protein vaccines. OVX836 is a recombinant protein vaccine, obtained by the fusion of the DNA sequence of the influenza A nucleoprotein (NP) to the DNA sequence of the OVX313 heptamerization domain. We previously demonstrated that OVX836 provides broad-spectrum protection against influenza viruses. Here, we show that OVX836 intramuscular (IM) immunization induces higher numbers of NP-specific IFNγ-producing CD8+ T-cells in the lung, compared to mutant NP (NPm) and wild-type NP (NPwt), which form monomeric and trimeric structures, respectively. OVX836 induces cytotoxic CD8+ T-cells and high frequencies of lung TRM CD8+ T-cells, while inducing solid protection against lethal influenza virus challenges for at least 90 days. Adoptive transfer experiments demonstrated that protection against diverse influenza subtypes is mediated by NP-specific CD8+ T-cells isolated from the lung and spleen following OVX836 vaccination. OVX836 induces a high number of NP-specific lung CD8+ TRM-cells for long-term protection against influenza viruses.

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Selective dependence on IL-7 for antigen-specific CD8 T cell responses during airway influenza infection

Scientific Reports ◽

10.1038/s41598-021-03936-y ◽

2022 ◽

Vol 12 (1) ◽

Author(s):

Abdalla Sheikh ◽

Jennie Jackson ◽

Hanjoo Brian Shim ◽

Clement Yau ◽

Jung Hee Seo ◽

...

Keyword(s):

T Cells ◽

Lymph Node ◽

T Cell ◽

Viral Infection ◽

Cd8 T Cells ◽

Mediastinal Lymph Node ◽

Influenza Infection ◽

Cd8 T Cell ◽

Cell Responses ◽

Deficient Mice

AbstractInterleukin-7 (IL-7) is a cytokine known for its importance in T cell development and survival. How IL-7 shapes CD8 T cell responses during an acute viral infection is less understood. We had previously shown that IL-7 signaling deficient mice have reduced accumulation of influenza-specific CD8 T cells following influenza infection. We sought to determine whether IL-7 affects early CD8 T cell expansion in the mediastinal lymph node and effector function in the lungs. Using IL-7Rα signaling deficient mice, we show that IL-7 is required for a normal sized mediastinal lymph node and the early clonal expansion of influenza-specific CD8 T cells therein. We show that IL-7 plays a cell-intrinsic role in the accumulation of NP366–374 and PA224–233-specific CD8 T cells in the lymph node. We also found that IL-7 shapes terminal differentiation, degranulation and cytokine production to a greater extent in PA224–233-specific than NP366–374-specific CD8 T cells. We further demonstrate that IL-7 is induced in the lung tissue by viral infection and we characterize multiple cellular sources that contribute to IL-7 production. Our findings on IL-7 and its effects on lower respiratory diseases will be important for expanding the utility of therapeutics that are currently available.

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Influenza infection results in local expansion of memory CD8+T cells with antigen non-specific phenotype and function

Clinical & Experimental Immunology ◽

10.1111/cei.12186 ◽

2013 ◽

Vol 175 (1) ◽

pp. 79-91 ◽

Cited By ~ 23

Author(s):

Gail D. Sckisel ◽

Julia K. Tietze ◽

Anthony E. Zamora ◽

Hua-Hui Hsiao ◽

Stephen O. Priest ◽

...

Keyword(s):

T Cells ◽

Cd8 T Cells ◽

Influenza Infection ◽

Memory Cd8 T Cells ◽

Local Expansion ◽

And Function

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Viral MHCI inhibition evades tissue-resident memory T cell formation and responses

Journal of Experimental Medicine ◽

10.1084/jem.20181077 ◽

2018 ◽

Vol 216 (1) ◽

pp. 117-132 ◽

Cited By ~ 5

Author(s):

Elvin J. Lauron ◽

Liping Yang ◽

Ian B. Harvey ◽

Dorothy K. Sojka ◽

Graham D. Williams ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Cd8 T Cells ◽

Viral Infections ◽

Cell Formation ◽

Memory Cd8 T Cells ◽

Effector Functions ◽

Cross Presentation ◽

Cognate Antigen

Tissue-resident memory CD8+ T cells (TRMs) confer rapid protection and immunity against viral infections. Many viruses have evolved mechanisms to inhibit MHCI presentation in order to evade CD8+ T cells, suggesting that these mechanisms may also apply to TRM-mediated protection. However, the effects of viral MHCI inhibition on the function and generation of TRMs is unclear. Herein, we demonstrate that viral MHCI inhibition reduces the abundance of CD4+ and CD8+ TRMs, but its effects on the local microenvironment compensate to promote antigen-specific CD8+ TRM formation. Unexpectedly, local cognate antigen enhances CD8+ TRM development even in the context of viral MHCI inhibition and CD8+ T cell evasion, strongly suggesting a role for in situ cross-presentation in local antigen-driven TRM differentiation. However, local cognate antigen is not required for CD8+ TRM maintenance. We also show that viral MHCI inhibition efficiently evades CD8+ TRM effector functions. These findings indicate that viral evasion of MHCI antigen presentation has consequences on the development and response of antiviral TRMs.

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Differential roles of migratory and resident DCs in T cell priming after mucosal or skin HSV-1 infection

Journal of Experimental Medicine ◽

10.1084/jem.20080601 ◽

2009 ◽

Vol 206 (2) ◽

pp. 359-370 ◽

Cited By ~ 109

Author(s):

Heung Kyu Lee ◽

Melodie Zamora ◽

Melissa M. Linehan ◽

Norifumi Iijima ◽

David Gonzalez ◽

...

Keyword(s):

T Cells ◽

Lymph Node ◽

T Cell ◽

Antigen Presentation ◽

Cd8 T Cells ◽

Mucosal Tissues ◽

Simplex Virus ◽

Needle Injection ◽

Hsv 1

Although mucosal surfaces represent the main portal of entry for pathogens, the mechanism of antigen presentation by dendritic cells (DCs) that patrol various mucosal tissues remains unclear. Instead, much effort has focused on the understanding of initiation of immune responses generated against antigens delivered by injection. We examined the contributions of migratory versus lymph node–resident DC populations in antigen presentation to CD4 and CD8 T cells after needle injection, epicutaneous infection, or vaginal mucosal herpes simplex virus (HSV) 1 infection. We show that upon needle injection, HSV-1 became lymph-borne and was rapidly presented by lymph node–resident DCs to CD4 and CD8 T cells. In contrast, after vaginal HSV-1 infection, antigens were largely presented by tissue-derived migrant DCs with delayed kinetics. In addition, migrant DCs made more frequent contact with HSV-specific T cells after vaginal infection compared with epicutaneous infection. Thus, both migrant and resident DCs play an important role in priming CD8 and CD4 T cell responses, and their relative importance depends on the mode of infection in vivo.

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Spatial, temporal and molecular dynamics of swine influenza virus-specific CD8 tissue resident memory T cells

10.1101/2021.08.23.457377 ◽

2021 ◽

Author(s):

Veronica Martini ◽

Matthew Edmans ◽

Simon Gubbins ◽

Siddharth Jayaraman ◽

Basu Paudyal ◽

...

Keyword(s):

Gene Expression ◽

T Cells ◽

Cd8 T Cells ◽

Influenza Infection ◽

Swine Influenza Virus ◽

Swine Influenza ◽

Effector Memory ◽

Local Immunity ◽

Memory Cd8 T Cells ◽

Mhc Tetramers

AbstractWe defined naïve, central memory, effector memory and terminally differentiated porcine CD8 T cells and analyzed their phenotype in lymphoid and respiratory tissues after influenza infection or immunization using peptide-MHC tetramers of three influenza nucleoprotein (NP) epitopes. The hierarchy of response to the three epitopes changes during the response in different tissues. Most NP-specific CD8 T cells in broncho-alveolar lavage (BAL) and lung are tissue resident memory cells (TRM), that express CD69 and have an effector memory or terminally differentiated phenotype. NP-specific cells isolated from BAL express genes characteristic of TRM, but gene expression differs at 7, 21 and 63 days post infection. The frequency of NP-specific cells declines over 63 days in all tissues but is best maintained in BAL. The pig is a powerful model for understanding how best to induce and harness local immunity to respiratory viruses.One sentence summaryInfluenza NP-specific porcine tissue resident memory CD8 T cells persist in the lung with major changes in gene expression.

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