Correction: Cross-presentation of a spread-defective MCMV is sufficient to prime the majority of virus-specific CD8+ T cells

Snyder, Christopher; Davis-Poynter, Nicholas; Farrell, Helen E.; Allan, Jane E.; Bonnett, Elizabeth L.; Doom, Carmen M.; Hill, Ann B.

doi:10.1371/journal.pone.0226705

Cited by 4 publications

(9 citation statements)

References 1 publication

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“…After recombination, an individual clone of the virus was selected that had lost the BAC sequences. Stocks of these viruses were generated in gL-3T3 cells, which provide gL in trans [ 7 , 38 ], and titered by plaque assay on gL-3T3s without centrifugal enhancement. Each individual ΔgL virus stock was checked for reversion by infecting BALB 3T3s, a non-complementing cell line, then passaging and monitoring these infected cells for 30 days to confirm that no further signs of infection developed as a result of cell to cell spread.…”

Section: Methodsmentioning

confidence: 99%

“…Traditionally, therefore, CMV was thought to provide just the right amount of antigen and inflammation to drive a maximal response [ 4 , 5 ]. However, the characteristic response to CMV occurs across the entire spectrum of virus activity–from the high virus load experienced by organ transplant patients [ 6 ], to undetectable virus following infection with a spread-deficient virus [ 7 ]. It seems likely, therefore, that some peculiar features of CMV’s immunogenicity during chronic infection are responsible for the characteristic T cell response.…”

Section: Introductionmentioning

confidence: 99%

“…One model proposes that T cell sensing of reactivation leads to silencing of viral activity, followed by a strong T-cell proliferative burst [ 19 ]. The entire scenario can be driven by minute amounts of latent virus [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

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Latent CMV infection of Lymphatic endothelial cells is sufficient to drive CD8 T cell memory inflation

et al. 2023

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CMV, a ubiquitous herpesvirus, elicits an extraordinarily large T cell response that is sustained or increases over time, a phenomenon termed ‘memory inflation.’ Remarkably, even latent, non-productive infection can drive memory inflation. Despite intense research on this phenomenon, the infected cell type(s) involved are unknown. To identify the responsible cell type(s), we designed a Cre-lox murine CMV (MCMV) system, where a spread-deficient (ΔgL) virus expresses recombinant SIINFEKL only in Cre+ host cells. We found that latent infection of endothelial cells (ECs), but not dendritic cells (DCs) or hepatocytes, was sufficient to drive CD8 T cell memory inflation. Infection of Lyve-1-Cre and Prox1-CreERT2 mice revealed that amongst EC subsets, infection of lymphatic ECs was sufficient. Genetic ablation of β2m on lymphatic ECs did not prevent inflation, suggesting another unidentified cell type can also present antigen to CD8 T cells during latency. This novel system definitively shows that antigen presentation by lymphatic ECs drives robust CD8 T cell memory inflation.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Latent CMV infection of Lymphatic endothelial cells is sufficient to drive CD8 T cell memory inflation

et al. 2023

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“…After recombination, an individual clone of the virus was selected that had lost the BAC sequences. Stocks of these viruses were generated in gL-3T3 cells, which provide gL in trans (Snyder et al, 2010; Snyder et al, 2019), and titered by plaque assay on gL-3T3s without centrifugal enhancement. Each individual ΔgL virus stock was checked for reversion by infecting BALB 3T3s, a non-complementing cell line, then passaging and monitoring these infected cells for 30 days to confirm that no further signs of infection developed as a result of cell to cell spread.…”

Section: Methodsmentioning

confidence: 99%

CD8 T Cell Memory Inflation is Driven by Latent CMV Infection of Lymphatic Endothelial Cells

Hill

Munks

Rott

et al. 2022

Preprint

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“…It is the current majority opinion in CMV immunology that the initiation of the CD8 T-cell response is primarily by antigen crosspresentation (33)(34)(35)(36)(37)(38). This view seems to be corroborated by the molecular explanation that the virus interferes with direct antigen presentation by expressing immune evasion proteins, which inhibit the transport of recently-loaded pMHC-I complexes to the cell surface and thereby prevent recognition by virus-specific CD8 T cells [(39), reviewed in (40)].…”

Section: Introductionmentioning

confidence: 99%

Modulation of cytomegalovirus immune evasion identifies direct antigen presentation as the predominant mode of CD8 T-cell priming during immune reconstitution after hematopoietic cell transplantation

Holtappels,

Büttner,

Freitag

et al. 2024

Front. Immunol.

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Cytomegalovirus (CMV) infection is the most critical infectious complication in recipients of hematopoietic cell transplantation (HCT) in the period between a therapeutic hematoablative treatment and the hematopoietic reconstitution of the immune system. Clinical investigation as well as the mouse model of experimental HCT have consistently shown that timely reconstitution of antiviral CD8 T cells is critical for preventing CMV disease in HCT recipients. Reconstitution of cells of the T-cell lineage generates naïve CD8 T cells with random specificities among which CMV-specific cells need to be primed by presentation of viral antigen for antigen-specific clonal expansion and generation of protective antiviral effector CD8 T cells. For CD8 T-cell priming two pathways are discussed: “direct antigen presentation” by infected professional antigen-presenting cells (pAPCs) and “antigen cross-presentation” by uninfected pAPCs that take up antigenic material derived from infected tissue cells. Current view in CMV immunology favors the cross-priming hypothesis with the argument that viral immune evasion proteins, known to interfere with the MHC class-I pathway of direct antigen presentation by infected cells, would inhibit the CD8 T-cell response. While the mode of antigen presentation in the mouse model of CMV infection has been studied in the immunocompetent host under genetic or experimental conditions excluding either pathway of antigen presentation, we are not aware of any study addressing the medically relevant question of how newly generated naïve CD8 T cells become primed in the phase of lympho-hematopoietic reconstitution after HCT. Here we used the well-established mouse model of experimental HCT and infection with murine CMV (mCMV) and pursued the recently described approach of up- or down-modulating direct antigen presentation by using recombinant viruses lacking or overexpressing the central immune evasion protein m152 of mCMV, respectively. Our data reveal that the magnitude of the CD8 T-cell response directly reflects the level of direct antigen presentation.

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Correction: Cross-presentation of a spread-defective MCMV is sufficient to prime the majority of virus-specific CD8+ T cells

Cited by 4 publications

References 1 publication

Latent CMV infection of Lymphatic endothelial cells is sufficient to drive CD8 T cell memory inflation

Latent CMV infection of Lymphatic endothelial cells is sufficient to drive CD8 T cell memory inflation

CD8 T Cell Memory Inflation is Driven by Latent CMV Infection of Lymphatic Endothelial Cells

Modulation of cytomegalovirus immune evasion identifies direct antigen presentation as the predominant mode of CD8 T-cell priming during immune reconstitution after hematopoietic cell transplantation

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