Dissecting CD8+ NKT Cell Responses to <i>Listeria</i> Infection Reveals a Component of Innate Resistance

Seregin, Sergey S.; Chen, Grace Y.; Laouar, Yasmina

doi:10.4049/jimmunol.1500084

Cited by 11 publications

(7 citation statements)

References 48 publications

(62 reference statements)

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“…Cluster 3 exclusively expressed CD9 and CD36, identifying these cells as NK-like CD8 cells. 76, 77 Clusters 7 and 13 were identified as NK-like T cells with a CD45RA+ terminally differentiated memory (EMRA) phenotype. Based on these markers, all CD8 T cell clusters were called ( Figure 3B ).…”

Section: Resultsmentioning

confidence: 99%

Combined protein and transcript single cell RNA sequencing in human peripheral blood mononuclear cells

Vallejo

Saigusa

Gulati

et al. 2020

Preprint

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Background: HIV-infected people have an increased risk of atherosclerosis-based cardiovascular disease (CVD), even when the HIV virus is fully controlled. Both chronic HIV infection and CVD are chronic inflammatory diseases. The interaction between these two diseases is not well understood. Methods: The Womens Interagency HIV Study (WIHS) collected peripheral blood mononuclear cells (PBMCs) and data on subclinical CVD defined by carotid artery ultrasound from HIV-infected women. We interrogated 32 PBMC samples using combined protein and transcript panel single cell (sc) RNA sequencing of women without HIV or CVD, with HIV only, with HIV and CVD, and with HIV and CVD treated with cholesterol-lowering drugs. Expression of 40 surface markers enabled detailed analysis of all major cell types, resolving 58 clusters in almost 42,000 single cells. Results: Many clusters including 5 of 8 classical monocyte clusters showed significantly different gene expression between the groups of participants, revealing the inflammatory signatures of HIV, CVD and their interactions. Genes highly upregulated by CVD included CCL3, CCL4 and IL-32, whereas CXCL2 and 3 were more highly upregulated by HIV. Many genes were synergistically upregulated by HIV and CVD, but others were antagonistically regulated, revealing that the gene signature in people with HIV and CVD is not simply the sum of the HIV and CVD signatures. Elevated expression of most inflammatory genes was reversed by cholesterol control (statin treatment). The cell numbers in 3 of 5 intermediate monocyte subsets, 1 of 14 CD8 T cell subsets, 1 of 6 B cell subsets and 1 of 6 NK cell subsets showed significant changes with HIV or CVD. Conclusions: We conclude that HIV and CVD show interactive inflammatory signatures including chemokines and cytokines that are improved by cholesterol-lowering drugs.

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Section: Resultsmentioning

confidence: 99%

Combined protein and transcript single cell RNA sequencing in human peripheral blood mononuclear cells

Vallejo

Saigusa

Gulati

et al. 2020

Preprint

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“…At the same time, other studies suggest that CD8 T-cells upregulate Ly49 receptors as a response to TCR or cytokine stimulation under certain conditions, either because of exposure to autoantigens ( 10 , 16 ) or during the antiviral response ( 13 , 15 , 31 , 32 ). There is data claiming that NK1.1 + CD8 T-cells include a significant fraction of Ly49 + cells and play an important role during the early stage of the immune response, show some innate-like features ( 33 , 34 ) and impact the anticancer immunity significantly ( 35 ).…”

Section: Discussionmentioning

confidence: 99%

Functional Characterization of Ly49+CD8 T-Cells in Both Normal Condition and During Anti-Viral Response

Shytikov

Rohila

et al. 2021

Front. Immunol.

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The role of Ly49+CD8 T-cells in the immune system is not clear. Previously, several papers suggested Ly49+CD8 T-cells as immunosuppressors, while multiple studies also suggested their role as potent participants of the immune response. The mechanism of Ly49 expression on CD8 T-cells is also not clear. We investigated phenotype, functions, and regulation of Ly49 expression on murine CD8 T-cells in both normal state and during LCMV infection. CD8 T-cells express different Ly49 receptors compared with NK-cells. In intact mice, Ly49+CD8 T-cells have a phenotype similar to resting central memory CD8 T-cells and do not show impaired proliferation and cytokine production. Conventional CD8 T-cells upregulate Ly49 receptors during TCR-induced stimulation, and IL-2, as well as IL-15, affect it. At the same time, Ly49+CD8 T-cells change the Ly49 expression profile dramatically upon re-stimulation downregulating inhibitory and upregulating activating Ly49 receptors. We observed the expression of Ly49 receptors on the virus-specific CD8 T-cells during LCMV infection, especially marked in the early stages, and participation of Ly49+CD8 T-cells in the anti-viral response. Thus, CD8 T-cells acquire Ly49 receptors during the T-cell activation and show dynamic regulation of Ly49 receptors during stimulation.

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“…55 CD8 + NKT cells, not CD8 + NK1.1 − cells, are able to proliferate independently from antigen stimulation and express IFN-γ and GzmB. 56 Based on these studies, the 'natural killer cell-mediated cytotoxicity' pathway may be involved in CD8-mediated biliary destruction. Type 2 CD8 + NKT cells may prime PBC-like disease in mice and even in PBC patients.…”

Section: Several Murine Models Of Autoimmune Cholangitis Have Attractmentioning

confidence: 99%

Proteomic analysis reveals distinctive protein profiles involved in CD8+ T cell-mediated murine autoimmune cholangitis

Zhang

et al. 2018

Cell Mol Immunol

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Autoimmune cholangitis arises from abnormal innate and adaptive immune responses in the liver, and T cells are critical drivers in this process. However, little is known about the regulation of their functional behavior during disease development. We previously reported that mice with T cell-restricted expression of a dominant negative form of transforming growth factor beta receptor type II (dnTGFβRII) spontaneously develop an autoimmune cholangitis that resembles human primary biliary cholangitis (PBC). Adoptive transfer of CD8 but not CD4 T cells into Rag1 mice reproduced the disease, demonstrating a critical role for CD8 T cells in PBC pathogenesis. Herein, we used SOMAscan technology to perform proteomic analysis of serum samples from dnTGFβRII and B6 control mice at different ages. In addition, we analyzed CD8 protein profiles after adoptive transfer of splenic CD8 cells into Rag1 recipients. The use of the unique SOMAscan aptamer technology revealed critical and distinct profiles of CD8 cells, which are key to biliary mediation. In total, 254 proteins were significantly increased while 216 proteins were significantly decreased in recipient hepatic CD8 cells compared to donor splenic CD8 cells. In contrast to donor splenic CD8 cells, recipient hepatic CD8 cells expressed distinct profiles for proteins involved in chemokine signaling, focal adhesion, T cell receptor and natural killer cell-mediated cytotoxicity pathways.

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Dissecting CD8+ NKT Cell Responses to Listeria Infection Reveals a Component of Innate Resistance

Cited by 11 publications

References 48 publications

Combined protein and transcript single cell RNA sequencing in human peripheral blood mononuclear cells

Combined protein and transcript single cell RNA sequencing in human peripheral blood mononuclear cells

Functional Characterization of Ly49+CD8 T-Cells in Both Normal Condition and During Anti-Viral Response

Proteomic analysis reveals distinctive protein profiles involved in CD8+ T cell-mediated murine autoimmune cholangitis

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