Infection of APC by Human Cytomegalovirus Controlled Through Recognition of Endogenous Nuclear Immediate Early Protein 1 by Specific CD4+ T Lymphocytes

Roy, Emmanuelle Le; Baron, Michel; Faigle, Wolfgang; Clément, D; Lewinsohn, David; Streblow, Daniel N.; Nelson, Jay A.; Amigorena, Sebastián; Davignon, J.

doi:10.4049/jimmunol.169.3.1293

Cited by 22 publications

(4 citation statements)

References 54 publications

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“…We also found that HCMV pp52 negative bystander DCs, which migrated toward CCL19, were very efficient stimulators of HCMV-specific CD4 ϩ T cells. This observation suggests that effective presentation of viral Ags, probably derived from the inoculum (23) in the absence of viral replication, is undisturbed, which may explain the high in vivo frequencies of HCMV Ag-specific CD4 ϩ T cells (29). The viral inhibition of the induction of CCR7 expression by DCs is the principal element in the impaired DC migration.…”

Section: Discussionmentioning

confidence: 94%

Impaired Lymphoid Chemokine-Mediated Migration due to a Block on the Chemokine Receptor Switch in Human Cytomegalovirus-Infected Dendritic Cells

Moutaftsi

Brennan

Spector

et al. 2004

J Virol

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Dendritic cell (DC) migration from the site of infection to the site of T-cell priming is a crucial event in the generation of antiviral T-cell responses. Here we present to our knowledge the first functional evidence that human cytomegalovirus (HCMV) blocks the migration of infected monocyte-derived DCs toward lymphoid chemokines CCL19 and CCL21. DC migration is blocked by viral impairment of the chemokine receptor switch at the level of the expression of CCR7 molecules. The inhibition occurs with immediate-early-early kinetics, and viral interference with NF-B signaling is likely to be at least partially responsible for the lack of CCR7 expression. DCs which migrate from the infected cultures are HCMV antigen negative, and consequently they do not stimulate HCMV-specific CD8 ؉ T cells, while CD4 ؉ -T-cell activation is not impaired. Although CD8 ؉ T cells can also be activated by alternative antigen presentation mechanisms, the spatial segregation of naive T cells and infected DCs seems a potent mechanism of delaying the generation of primary CD8 ؉ -T-cell responses and aiding early viral spread.

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Section: Discussionmentioning

confidence: 94%

Impaired Lymphoid Chemokine-Mediated Migration due to a Block on the Chemokine Receptor Switch in Human Cytomegalovirus-Infected Dendritic Cells

Moutaftsi

Brennan

Spector

et al. 2004

J Virol

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“…Frequencies of CMV-specific CD4 pos and CD8 pos T-cells have been shown to be extremely high in immunocompetent persons [17], and to be maintained throughout life [20]. Contributions of CD4 pos and CD8 pos T cells have been demonstrated both in vitro [21,22] and in vivo , [23,24]. …”

Section: Introductionmentioning

confidence: 99%

“…Although CD4 pos T cells possess their own capacity to inhibit CMV replication [21,22,25], they also contribute to the differentiation and maintenance of CMV-specific CD8 pos T cells [23]. Moreover, anti-CMV specific effectors are increased in CD28 neg CD4 pos T cells [17,26], a population that is expanded in RA, because of TNF-α [27,28].…”

Section: Introductionmentioning

confidence: 99%

Maintenance of cytomegalovirus-specific CD4pos T-cell response in rheumatoid arthritis patients receiving anti-tumor necrosis factor treatments

Davignon

Boyer

Jamard³

et al. 2010

Arthritis Res Ther

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IntroductionAnti-tumor necrosis factor (TNF)-α biotherapies have considerably changed the treatment of rheumatoid arthritis (RA). However, serious infections are a major concern in patients with rheumatic diseases treated with anti-TNF-α. Little is known about viral, especially latent, infections in anti-TNF-α treatments. Infections by cytomegalovirus (CMV), a β-herpes virus, are frequent and induce a strong CD4pos T-cell immunity, which participates in the control of infection. We thus have chosen to analyze the CD4pos T-cell response to CMV antigens as a model of antiviral response in RA patients treated with anti-TNF-α. CD28 expression was evaluated.MethodsWe have measured the CD4pos response to CMV antigens in RA patients, before and after initiation of treatment with an anti-TNF-α agent. The intracellular production of interferon (IFN)-γ in total and CD28neg CD4pos T cells in response to CMV antigens (Ags) was evaluated with flow cytometry. The proliferation of total CD4pos T cells in the presence of CMV antigens was measured with 3H-thymidine incorporation.ResultsAnti-TNF-α treatments impaired neither the anti-CD4pos anti-CMV IFN-γ response nor the proliferative response in patients. The percentage of CD28neg CD4pos cells remained constant.ConclusionsOur data suggest that the CD4pos T-cell response against CMV is not altered by anti-TNF-α treatments and that infection remains controlled in treated RA patients latently infected with CMV. Our observation brings new insight into the current knowledge of the risks of infection in patients treated with anti-TNF-α biotherapies.

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“…In this compartment, viral peptides can be bound by MHC‐II molecules, either newly synthesized or recycling from the cell surface (8, 39), and be expressed on the cell surface where they can be recognized by CD4 + T cells. These T cells can mediate a direct sterilization of the reservoir of infection through an intrinsic cytotoxic function (40), or through secretion of cytokines that enhance cellular antiviral function. For instance, IFN‐γ induces expression of 2′,5′‐oligoadenlyate synthetase that mediates degradation of viral RNA (41).…”

Section: Identification Of the Cellular Reservoir Of Infectionmentioning

confidence: 99%

MHC immunoevasins: protecting the pathogen reservoir in infection

et al. 2005

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Alteration of antigen recognition by T cells as result of insufficient major histocompatibility complex (MHC)-dependent antigen-presenting function has been observed in many cases of infections, particularly in in vitro systems. To hide themselves from an efficient immune response, pathogens may act on MHC-related functions at three levels: (i) by limiting the number of potential antigens that can be presented to naïve T cells; (ii) by synthesizing proteins which directly affect MHC cell-surface expression; and (iii) by altering the normal intracellular pathway of peptide loading on MHC. Here, we review examples of pathogens' action on each single step of MHC function and we suggest that the result of these often synergistic actions is both a limitation of the priming of naïve T cells and, more importantly, a protection of the pathogen's reservoir from the attack of primed T cells. The above mechanisms may also generate a skewing effect on immune effector mechanisms, which helps preserving the reservoir of infection from sterilization by the immune system.

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Infection of APC by Human Cytomegalovirus Controlled Through Recognition of Endogenous Nuclear Immediate Early Protein 1 by Specific CD4+ T Lymphocytes

Cited by 22 publications

References 54 publications

Impaired Lymphoid Chemokine-Mediated Migration due to a Block on the Chemokine Receptor Switch in Human Cytomegalovirus-Infected Dendritic Cells

Impaired Lymphoid Chemokine-Mediated Migration due to a Block on the Chemokine Receptor Switch in Human Cytomegalovirus-Infected Dendritic Cells

Maintenance of cytomegalovirus-specific CD4pos T-cell response in rheumatoid arthritis patients receiving anti-tumor necrosis factor treatments

MHC immunoevasins: protecting the pathogen reservoir in infection

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