T inflammatory memory CD8 T cells participate to antiviral response and generate secondary memory cells with an advantage in XCL1 production

Jubin, V.; Ventre, Erwan; Leverrier, Yann; Djebali, Sophia; Mayol, Katia; Tomkowiak, Martine; Mafille, Julien; Teixeira, Marie; Teoh, Denise; Lina, Bruno; Walzer, Thierry; Arpin, Christophe; Marvel, Jacqueline

doi:10.1007/s12026-012-8340-4

Cited by 21 publications

(19 citation statements)

References 53 publications

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“…Antigen-specific TIM cells were generated in a sterile inflammatory context by direct immunization of F5 TCR transgenic mice with the antigenic NP68 peptide in saline202122. Flu-induced memory cells (Flu-TM) were generated by intranasal infection with influenza virus expressing the NP68 epitope of C57BL/6 J mice that were grafted with 2 × 10 5 naive F5 CD8 T cells.…”

Section: Resultsmentioning

confidence: 99%

“…A broad comparison of the memory cells induced by these two types of immunization opens an avenue for identifying genes that can be associated with protection. In order to characterise transcriptomic properties of protective memory cells, we have compared memory CD8 cells generated in response to NP68 encoding influenza virus (Flu-TM) to T Inflammatory memory (TIM) cells that were generated by NP68 peptide in a sterile inflammatory context202122. Since high affinity TCRs have been associated with memory response efficiency, we generated memory cell types using naive CD8 T cells harbouring the same antigenic specificity, using F5 TCR transgenic cells that are specific for NP68, an influenza nucleoprotein epitope.…”

mentioning

confidence: 99%

“…This system avoids the selection of CD8 T cell clones with different affinities in the different experimental models. TIM CD8 T cells display classic phenotypic and functional memory traits202122. We have compared the capacity of these two subsets of memory cells to protect against a lethal dose of influenza virus.…”

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confidence: 99%

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Immune signatures of protective spleen memory CD8 T cells

Brinza

Djebali

Tomkowiak

et al. 2016

Sci Rep

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Memory CD8 T lymphocyte populations are remarkably heterogeneous and differ in their ability to protect the host. In order to identify the whole range of qualities uniquely associated with protective memory cells we compared the gene expression signatures of two qualities of memory CD8 T cells sharing the same antigenic-specificity: protective (Influenza-induced, Flu-TM) and non-protective (peptide-induced, TIM) spleen memory CD8 T cells. Although Flu-TM and TIM express classical phenotypic memory markers and are polyfunctional, only Flu-TM protects against a lethal viral challenge. Protective memory CD8 T cells express a unique set of genes involved in migration and survival that correlate with their unique capacity to rapidly migrate within the infected lung parenchyma in response to influenza infection. We also enlighten a new set of poised genes expressed by protective cells that is strongly enriched in cytokines and chemokines such as Ccl1, Ccl9 and Gm-csf. CCL1 and GM-CSF genes are also poised in human memory CD8 T cells. These immune signatures are also induced by two other pathogens (vaccinia virus and Listeria monocytogenes). The immune signatures associated with immune protection were identified on circulating cells, i.e. those that are easily accessible for immuno-monitoring and could help predict vaccines efficacy.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

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Immune signatures of protective spleen memory CD8 T cells

Brinza

Djebali

Tomkowiak

et al. 2016

Sci Rep

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“…All Abs were from BD Biosciences, eBioscience, and R&D Systems, except the anti-mCCL5 mouse mAb that was produced in house (30). The F5-TCR was detected with NP68-conjugated H-2D b allophycocyanin tetramers from ProImmune.…”

Section: Mabs and Flow Cytometrymentioning

confidence: 99%

Negative Regulation of NKG2D Expression by IL-4 in Memory CD8 T Cells

Ventre

Brinza

Schicklin

et al. 2012

The Journal of Immunology

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IL-4 is one of the main cytokines produced during Th2-inducing pathologies. This cytokine has been shown to affect a number of immune processes such as Th differentiation and innate immune responses. However, the impact of IL-4 on CD8 T cell responses remains unclear. In this study, we analyzed the effects of IL-4 on global gene expression profiles of Ag-induced memory CD8 T cells in the mouse. Gene ontology analysis of this signature revealed that IL-4 regulated most importantly genes associated with immune responses. Moreover, this IL-4 signature overlapped with the set of genes preferentially expressed by memory CD8 T cells over naive CD8 T cells. In particular, IL-4 downregulated in vitro and in vivo in a STAT6-dependent manner the memory-specific expression of NKG2D, thereby increasing the activation threshold of memory CD8 T cells. Furthermore, IL-4 impaired activation of memory cells as well as their differentiation into effector cells. This phenomenon could have an important clinical relevance as patients affected by Th2 pathologies such as parasitic infections or atopic dermatitis often suffer from viral-induced complications possibly linked to inefficient CD8 T cell responses.

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“…O. Ferraris and M. Ottmann in Pr. B. Lina's laboratory (Jubin et al, 2012). VV-NP was constructed and produced by Dr. D.Y.L.…”

Section: Experimental Workmentioning

confidence: 99%

Predicting pathogen-specific CD8 T cell immune responses from a modeling approach

Crauste

Terry

Mercier

et al. 2015

Journal of Theoretical Biology

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The primary CD8 T cell immune response constitutes a major mechanism to fight an infection by intra-cellular pathogens. We aim at assessing whether pathogen-specific dynamical parameters of the CD8 T cell response can be identified, based on measurements of CD8 T cell counts, using a modeling approach. We generated experimental data consisting in CD8 T cell counts kinetics during the response to three different live intra-cellular pathogens: two viruses (influenza, vaccinia) injected intranasally, and one bacteria (Listeria monocytogenes) injected intravenously. All pathogens harbor the same antigen (NP68), but differ in their interaction with the host. In parallel, we developed a mathematical model describing the evolution of CD8 T cell counts and pathogen amount during an immune response. This model is characterized by 9 parameters and includes relevant feedback controls. The model outputs were compared with the three data series and an exhaustive estimation of the parameter values was performed. By focusing on the ability of the model to fit experimental data and to produce a CD8 T cell population mainly composed of memory cells at the end of the response, critical parameters were identified. We show that a small number of parameters (2-4) define the main features of the CD8 T cell immune response and are characteristic of a given pathogen. Among these parameters, two are related to the effector CD8 T cell mediated control of cell and pathogen death. The parameter associated with memory cell death is shown to play no relevant role during the main phases of the CD8 T cell response, yet it becomes essential when looking at the predictions of the model several months after the infection.

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T inflammatory memory CD8 T cells participate to antiviral response and generate secondary memory cells with an advantage in XCL1 production

Cited by 21 publications

References 53 publications

Immune signatures of protective spleen memory CD8 T cells

Immune signatures of protective spleen memory CD8 T cells

Negative Regulation of NKG2D Expression by IL-4 in Memory CD8 T Cells

Predicting pathogen-specific CD8 T cell immune responses from a modeling approach

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