Activation of influenza virus–specific CD4+ and CD8+ T cells: a new role for plasmacytoid dendritic cells in adaptive immunity

Fonteneau, Jean-François; Gilliet, Michel; Larsson, Marie; Dasilva, Ida; Münz, Christian; Liu, Yongjun; Bhardwaj, Nina

doi:10.1182/blood-2002-10-3063

Cited by 299 publications

(279 citation statements)

References 34 publications

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“…In this context, in the absence of human serum, the capture of the antigen could involve pinocytosis rather than receptor-mediated endocytosis. This mechanism of antigen capture may be different from the up-take of viral antigens that need membrane interactions for internalization [22]. We next show that LPDC exposed to influenza virus induce CD8 + clone activation, as evidenced by the lysis of infected or peptide-pulsed LPDC, and the secretion of IFN-+ (not shown).…”

Section: Discussionmentioning

confidence: 87%

See 1 more Smart Citation

Leukemic plasmacytoid dendritic cells share phenotypic and functional features with their normal counterparts

Chaperot¹,

Perrot²,

Jacob³

et al. 2004

Eur J Immunol

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This work aims to further characterize the newly described leukemic plasmacytoid dendritic cells (LPDC), for which we had previously demonstrated their normal, PDC-like ability to produce IFN- § . In addition, LPDC also express the specific antigens BDCA-2 and BDCA-4. Importantly, they become fully competent antigen-presenting cells (APC) after a short maturation induced by IL-3 + CD40L or virus, exhibiting a characteristic APC phenotype (high expression of CD83 and of the costimulatory molecules CD40, CD80, CD86). Whereas IL-3 + CD40L-activated LPDC prime naive CD4 + T cells towards a Th2 pathway (IL-4-secreting T cells), virus-activated LPDC drive a Th1 profile (IFN-+ -secreting T cells). Moreover, we show in one case that LPDC are able to capture, process and present exogenous antigens, leading to the activation of both CD4 + and CD8 + T cell clones in an antigen-specific manner. This study further characterizes the phenotype and immunological functions of LPDC.

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Section: Discussionmentioning

confidence: 87%

“…However, the involvement of PDC in the adaptative anti-viral immune response has just recently been investigated. PDC, like MDC, are able to acquire, process and present viral antigens to induce the proliferation and differentiation of anti-virus CD8 + and CD4 + T cells [22].…”

Section: Introductionmentioning

confidence: 99%

Leukemic plasmacytoid dendritic cells share phenotypic and functional features with their normal counterparts

Chaperot¹,

Perrot²,

Jacob³

et al. 2004

Eur J Immunol

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show abstract

“…Other viral antigens have also been shown to be cross-presented in vitro including vaccinia virus, canarypox virus, HIV and HCMV, amongst others [78][79][80][81][82][83]. This crosspresentation suggests a mechanism for the antigen transfer between DC subtypes observed in murine models and suggests that the immunoevasive mechanisms of costimulatory molecule downregulation and apoptosis of DC by HSV can be counteracted by uptake by bystander DC.…”

Section: Subsets In Innate and Adaptive Immunity To Hsvmentioning

confidence: 94%

Langerhans cells and viral immunity

2008

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Langerhans cells (LC) are a unique dendritic cell subset that are located in mucosal stratified squamous epithelium and skin epidermis. Their location is ideally suited for their function as antigen presenting cells that capture invading viruses and induce anti-viral immunity. However, it is becoming evident that the interaction between LC and viruses can result in different responses, depending on the virus and the receptors involved. Here we will discuss the recent data on the similarities and differences in roles of LC in viral immunity to and infection with HIV, herpes simplex and varicella-zoster virus. Although all three viruses interact with LC during initial infection, the effects can be quite different, reflecting differences in biology and pathogenesis. Key words: Dendritic cells Á Langerhans cells Á Infectious diseases Á HIV Á HerpesvirusesSee accompanying mini-review by Kaplan et al. Biology of LC and interactions with virusesThe resident epidermal dendritic cells (DC), Langerhans cells (LC), form a tight network with each other and with the surrounding keratinocytes via E-cadherin in the skin or mucosal stratified squamous epithelium. In the anogenital region they are distributed throughout the anogenital skin and mucosa including vagina, ectocervix as well as male foreskin. In stratified squamous epithelium, LC overlie interstitial or dermal DC [1]. LC can repopulate from local and blood-borne precursors (reviewed by Kaplan et al. in this issue [2]). Similar to other myeloid DC, LC are able to bridge innate and adaptive immunity. They are able to interact directly with microorganisms at the periphery to produce effector cytokines and initiate or restimulate activation of T and B lymphocytes through antigen presentation. LC express different pattern recognition receptors such as C-type lectin receptors (CLR) and Toll-like receptors (TLR), to bind and capture pathogens. These interactions result in activation of intracellular signalling pathways leading to LC activation and cytokine induction. The CLR expressed by skin DC differ by site: Langerin by epidermal LC and DC-SIGN and mannose receptor by dermal DC. LC like other migratory DC are in an immature, highly endocytic state while sessile in the skin/mucosa. However after pathogen binding to TLR and uptake, LC become mature and migratory, downregulating their endocytic and antigen processing capacity. Mature LC migrate to the lymph nodes where they are directly or indirectly involved in presentation of pathogenderived antigens on MHC Class I and II to T cells, resulting in activation of antigen-specific T cells [2][3][4]. Recent studies have raised the possibility that LC may have an immunosuppressive role [5][6][7]. Kaplan et al. [2] showed that contact hypersensitivity was amplified on LC ablation, while Cumberbatch et al.[5] found defective LC mobilisation in patients with psoriasis. Immunosuppression rather than stimulation could be explained, in part, by the maturational process associated with LC migration during steady-state conditions. Jian...

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“…74 Such activated pDCs were shown to induce the expansion of influenza-specific CD4 + and CD8 + T cells. 91 Supporting the notion that pDCs have to be conditioned to act as APCs, pDCs pulsed with an immuno-dominant LCMV (lymphocytic choriomeningitis virus) peptide fail to prime TCR-transgenic CD8 + T cells. By contrast, after infection of mice with unrelated virus, GP 33À41 -pulsed pDCs induced robust CD8 + T-cell proliferation and a potent in vitro T H 1 polarization.…”

Section: Functions By Conditional Cell Ablationmentioning

confidence: 98%

Probing in vivo dendritic cell functions by conditional cell ablation

Sapoznikov

2008

Immunol Cell Biol

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Dendritic cells (DCs) play a central role in T-cell activation and the control of the inherent autoreactivity of the T-cell compartment. Pleiotropic DC functions are likely associated with discrete DC subsets. However, the latter remain largely defined by phenotype and unique anatomic location, rather than function. The investigation of DC involvement in complex phenomena that rely on multicellular interactions, such as immuno-stimulation and tolerization calls for an assessment of DC functions within physiological context. Given the highly dynamic DC compartment, the method of choice to study in vivo DC functions is their conditional ablation in the intact organism. Here, we summarize the recent progress in this field highlighting pitfalls and prospects of the approach.

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Activation of influenza virus–specific CD4+ and CD8+ T cells: a new role for plasmacytoid dendritic cells in adaptive immunity

Cited by 299 publications

References 34 publications

Leukemic plasmacytoid dendritic cells share phenotypic and functional features with their normal counterparts

Leukemic plasmacytoid dendritic cells share phenotypic and functional features with their normal counterparts

Langerhans cells and viral immunity

Probing in vivo dendritic cell functions by conditional cell ablation

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