CD8+ T Cells Specific for EBV, Cytomegalovirus, and Influenza Virus Are Activated during Primary HIV Infection

Doisne, Jean‐Marc; Urrutia, Alejandra; Lacabaratz, Christine; Goujard, Cécile; Meyer, Laurence; Chaix, Marie‐Laure; Sinet, Martine; Venet, Alain

doi:10.4049/jimmunol.173.4.2410

Cited by 174 publications

(161 citation statements)

References 62 publications

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“…Antigen-specific cells initially displayed an effector cell phenotype and gradually developed into YFV-17D-specific memory CD8 + T cells [10]. In contrast to other studies, no significant activation of CD8 + T cells for other viruses such as EBV could be detected [11]. In summary, YFV-17D vaccination induces a specific and protective adaptive immune response, including the generation of cytotoxic T cells, a heterogeneous TH-cell profile and potent neutralizing antibodies.…”

Section: Introductionmentioning

confidence: 65%

The early cellular signatures of protective immunity induced by live viral vaccination

et al. 2012

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Here, we have used primary vaccination of healthy donors with attenuated live yellow fever virus 17D (YFV-17D) as a model to study the generation of protective immunity. In short intervals after vaccination, we analyzed the induction of YFV-17D specific T-and B-cell immunity, bystander activation, dendritic cell subsets, changes in serum cytokine levels, and YFV-17D-specific antibodies. We show activation of innate immunity and a concomitant decline of numbers of peripheral blood T and B cells. An early peak of antigen-specific T cells at day 2, followed by mobilization of innate immune cells, preceded the development of maximal adaptive immunity against YFV-17D at day 14 after vaccination. Interestingly, potent adaptive immunity as measured by high titers of neutralizing YFV-17D-specific antibodies, correlated with early activation and recruitment of YFV-17D-specific CD4 + T cells and higher levels of sIL-6R. Thus our data might provide new insights into the interplay of innate and adaptive immunity for the induction of protective immunity. Keywords: Immune responses r Protective immunity r T cells r Vaccination r Yellow fever virus Supporting Information available online IntroductionVaccines were introduced into modern medicine about 300 years ago and are now administered to millions of people every year, conferring efficient protection against a variety of toxins as well as bacterial and viral diseases. However, the complex interplay of innate and adaptive immune cells, particularly in the first few Correspondence: Dr. Siegfried Kohler e-mail: siegfried.kohler@charite.de days after vaccination, leading to protective immunity after challenge with an innocuous agent is still incompletely understood. Yet this information might be crucial to developing new vaccines or improving current vaccinations with respect to efficiency, especially in risk groups and prevention of side effects.In order to assess early events in the course of a defined protective immune response, we studied vaccination of healthy * These authors contributed equally to this work. Eur. J. Immunol. 2012. 42: 2363-2373 humans with the 17D yellow fever virus vaccine (YFV-17D 5] and efficiently induce DC maturation, characterized by upregulation of CD86, CD80, MHC class II, and CD40. Barba-Spaeth et al. detected YFV-17D-dependent infection of human DCs irrespective of their maturation state but no infection of monocytes [6]. In vivo, the activation of B-and T cells has been shown to occur between day 4 and day 15 in YFV-17D vaccinated subjects, characterized by the expression of phenotypic markers such as CD69 or IL-10-R on CD8 + T and B cells and HLA-DR on CD4 + T cells [7]. A persistent, broadly reactive CD4 + T-cell response with a mixed TH1/TH2 phenotype was observed [8]. The maximal expansion of CD8 + T cells was detectable at day 30 with 0.5 to 17% of CD8 + T cells recognized by tetramers, yet activation determined by expression of HLA-DR + , CD38 + , KI-67 high , and BCL-2 low , among YFV-17D-specific CD8 + T cells was already detected at ...

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Section: Introductionmentioning

confidence: 65%

The early cellular signatures of protective immunity induced by live viral vaccination

et al. 2012

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“…This has been shown with herpesvirus infections, either due to cross-recognition of epitopes or through bystander activation mediated by the cytokine environment (28,47,48). Specific memory T cells could also be activated as a result of reactivating latent pathogen.…”

Section: Discussionmentioning

confidence: 99%

“…Specific memory T cells could also be activated as a result of reactivating latent pathogen. Although CMV may reactivate as a consequence of cytokine-driven differentiation of myeloid cells (20), reactivation is not necessary to activate CMV-specific T cells in acute EBV, HIV, or hepatitis B virus infection (28,48,49). Collectively, these studies suggest that the activation of pre-existing memory cells could be important for the course of a secondary infection and for T cell homeostasis (discussed in Ref.…”

Section: Discussionmentioning

confidence: 99%

Cytomegalovirus-Seropositive Children Show Inhibition of In Vitro EBV Infection That Is Associated with CD8+CD57+ T Cell Enrichment and IFN-γ

Sohlberg

Saghafian–Hedengren

Rasul

et al. 2013

The Journal of Immunology

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EBV, a human herpesvirus, is commonly acquired during childhood and persists latently in B cells. EBV seropositivity has been connected to immunomodulatory effects such as altered T and NK cell functional responses as well as protection against early IgE sensitization; however, owing to the asymptomatic presentation during childhood little is known regarding the infection process in children of different ages. In this study, we used mononuclear cells from cord blood and from 2- and 5-y-old EBV-naive children for in vitro EBV infection. We show that the degree of EBV-induced B cell activation and expansion differs between age groups and in particular in relationship to IFN-γ production capacity. EBV infection induced redistribution between B cell subsets with enrichment of IgD+CD27+ cells (commonly referred to as non–switched memory) in infected cord blood cell cultures, and of IgD−CD27+ cells (switched memory) in cell cultures from older children. We also related results to serostatus to CMV, a persistent herpesvirus that can affect differentiation status of T and NK cells. As compared with CMV− children, the EBV-induced enrichment of IgD−CD27+ B cells was significantly reduced in infected cell cultures from CMV+ children. This effect was associated with high levels of IFN-γ and frequencies of highly mature CD8+CD57+ T cells in CMV+ children. Our results demonstrate that both a child’s age and serostatus to CMV will have an impact on EBV-induced B cell activation and expansion, and they point to the ability of viruses with immunomodulatory functions, such as CMV, to affect immune responses within the host system.

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“…These observations suggest that bystander activation is prevalent during the early stages (<7 days) of influenza infection. Antigen non-specific bystander activation has been well documented in a number of viral infections [12,28], including influenza [29,30]. While others have observed bystander activation, little is known about the specific phenotype and/or function of these cells during infections.…”

Section: Phenotype Of Cd8 + T Cells After Primary Influenza Infectionmentioning

confidence: 99%

“…Other studies using tetramers have revealed much higher antigenspecific responses in certain viral models; up to 80% of CD8 + T cells in the spleen of lymphochoriomeningovirus (LCMV)-infected mice have been shown to be specific for 10 different LCMV-derived epitopes at the peak of primary infection [9][10][11]. Another study investigating newly HIV-infected humans showed activation of approximately 50% of the circulating T cells, only about 1% of which were HIVspecific [12]. During influenza infection, it has been observed that up to 70% of lung infiltrating CD8 + T cells showed signs of activation, whereas only 30% of those CD8 + T cells also stained positive for specific major histocompatibility complex (MHC) tetramers, given the current repertoire of known viral epitopes [13].…”

Section: Introductionmentioning

confidence: 99%

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

Sckisel

Tietze

Zamora

et al. 2013

Clinical and Experimental Immunology

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Summary Primary viral infections induce activation of CD8+ T cells responsible for effective resistance. We sought to characterize the nature of the CD8 + T cell expansion observed after primary viral infection with influenza. Infection of naive mice with different strains of influenza resulted in the rapid expansion of memory CD8 + T cells exhibiting a unique bystander phenotype with significant up-regulation of natural killer group 2D (NKG2D), but not CD25, on the CD44 high CD8+ T cells, suggesting an antigen non-specific phenotype. We further confirmed the non-specificity of this phenotype on ovalbuminspecific (OT-I) CD8 + T cells, which are not specific to influenza. These nonspecific CD8 + T cells also displayed increased lytic capabilities and were observed primarily in the lung. Thus, influenza infection was shown to induce a rapid, antigen non-specific memory T cell expansion which is restricted to the specific site of inflammation. In contrast, CD8 + T cells of a similar phenotype could be observed in other organs following administration of systemic agonistic anti-CD40 and interleukin-2 immunotherapy, demonstrating that bystander expansion in multiple sites is possible depending on whether the nature of activation is either acute or systemic. Finally, intranasal blockade of NKG2D resulted in a significant increase in viral replication early during the course of infection, suggesting that NKG2D is a critical mediator of anti-influenza responses prior to the initiation of adaptive immunity. These results characterize further the local bystander expansion of tissue-resident, memory CD8 + T cells which, due to their early induction, may play an important NKG2D-mediated, antigen non-specific role during the early stages of viral infection.

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CD8+ T Cells Specific for EBV, Cytomegalovirus, and Influenza Virus Are Activated during Primary HIV Infection

Cited by 174 publications

References 62 publications

The early cellular signatures of protective immunity induced by live viral vaccination

The early cellular signatures of protective immunity induced by live viral vaccination

Cytomegalovirus-Seropositive Children Show Inhibition of In Vitro EBV Infection That Is Associated with CD8+CD57+ T Cell Enrichment and IFN-γ

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

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