CD4-Independent Protective Cytotoxic T Cells Induced in Early Life by a Non-Replicative Delivery System Based on Virus-like Particles

Martínez, Xavier; Regner, Matthias; Kovařík, Jiří; Zarei, Shohreh; Hauser, Conrad; Lambert, Paul‐Henri; Siegrist, Claire‐Anne

doi:10.1006/viro.2002.1775

Cited by 18 publications

(22 citation statements)

References 54 publications

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“…However, in contrast to these reports, peptide-pulsed neonatal CD11c ϩ DC efficiently primed specific CTL responses when injected to adult mice (19) and nonreplicative virus-like particles elicited adult-like neonatal CD8 ϩ cell responses within 2 wk after priming, in absence of adjuvant (20).…”

contrasting

confidence: 77%

“…Equal numbers of splenocytes from individual mice were pooled 2 wk postimmunization and cultured as bulk or under limiting dilution conditions essentially as described (20). For bulk cultures, splenocytes were pooled by immunization groups and restimulated in vitro for 5 days with the LCMV 118 -132 or the HIV 315-329 peptide, followed by a 4-h 51 Cr-release assay with peptide-pulsed or unpulsed P815 target cells.…”

Section: Quantification Of Cytotoxic Responses and Ctl Precursor Freqmentioning

confidence: 99%

“…For assessment of CTL avidity, dose-response curves were measured with titrated amounts of peptide pulsed on target cells, and the data was normalized to maximal response, according to the formula 100/(lysis at maximum peptide concentration Ϫ lysis without peptide) ϫ (sample lysis Ϫ lysis without peptide). For limiting dilution analysis, titrated responder splenocytes were cultured for 10 days with 5 ϫ 10 5 irradiated syngeneic stimulator spleen cells, peptide, and IL-2 as described (20), followed by a 4-h 51 Cr-release assay of individual wells against peptide-pulsed P815 target cells.…”

Section: Quantification Of Cytotoxic Responses and Ctl Precursor Freqmentioning

confidence: 99%

“…The ELISPOT assay for detection of peptide-specific IFN-␥ secreting T cells was performed essentially as described (20). For analysis of ex vivo cytokine secretion, splenocytes were incubated for 48 h in ELISPOT plates with IL-2 and 10 6 irradiated (3000 rad) syngeneic splenocytes in the presence or absence of specific peptide.…”

Section: Elispot Assay Of Peptide-specific Cd8 ϩ T Cells Producing Ifn-␥mentioning

confidence: 99%

“…For in vitro analysis, splenocytes from 5-day restimulated cultures used for cytotoxicity assay were cultured for 24 h in ELISPOT plates with IL-2 and peptide-pulsed or -unpulsed irradiated syngeneic splenocytes. Processing and counting were performed as previously described (20). The proportion of CD8 ϩ splenocytes was determined by flow cytometry before start of the incubation in ELISPOT plates.…”

Section: Elispot Assay Of Peptide-specific Cd8 ϩ T Cells Producing Ifn-␥mentioning

confidence: 99%

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Partial Activation of Neonatal CD11c+ Dendritic Cells and Induction of Adult-Like CD8+ Cytotoxic T Cell Responses by Synthetic Microspheres

Regner

Martínez

Belnoue

et al. 2004

The Journal of Immunology

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Neonatal cytotoxic T cell responses have only been elicited to date with immunogens or delivery systems inducing potent direct APC activation. To define the minimal activation requirements for the induction of neonatal CD8+ cytotoxic responses, we used synthetic microspheres (MS) coated with a single CD8+ T cell peptide from lymphocytic choriomeningitis virus (LCMV) or HIV-1. Unexpectedly, a single injection of peptide-conjugated MS without added adjuvant induced CD4-dependent Ag-specific neonatal murine cytotoxic responses with adult-like CTL precursor frequency, avidity for Ag, and frequency of IFN-γ-secreting CD8+ splenocytes. Neonatal CD8+ T cell responses to MS-LCMV were elicited within 2 wk of a single immunization and, upon challenge, provided similar protection from viral replication as adult CTLs, demonstrating their in vivo competence. As previously reported, peptide-coated MS elicited no detectable activation of adult CD11c+ dendritic cells (DC). In contrast, CTL responses were associated with a partial activation of neonatal CD11c+ DC, reflected by the up-regulation of CD80 and CD86 expression but no concurrent changes in MHC class II or CD40 expression. However, this partial activation of neonatal DC was not sufficient to circumvent the requirement for CD4+ T cell help. The effective induction of neonatal CD8+ T cell responses by this minimal Ag delivery system demonstrates that neonatal CD11c+ DC may mature sufficiently to stimulate naive CD8+ neonatal T cells, even in the absence of strong maturation signals.

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contrasting

confidence: 77%

Section: Quantification Of Cytotoxic Responses and Ctl Precursor Freqmentioning

confidence: 99%

Section: Quantification Of Cytotoxic Responses and Ctl Precursor Freqmentioning

confidence: 99%

Section: Elispot Assay Of Peptide-specific Cd8 ϩ T Cells Producing Ifn-␥mentioning

confidence: 99%

Section: Elispot Assay Of Peptide-specific Cd8 ϩ T Cells Producing Ifn-␥mentioning

confidence: 99%

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Partial Activation of Neonatal CD11c+ Dendritic Cells and Induction of Adult-Like CD8+ Cytotoxic T Cell Responses by Synthetic Microspheres

Regner

Martínez

Belnoue

et al. 2004

The Journal of Immunology

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Protective anti‐mycobacterial T cell responses through exquisite in vivo activation of vaccine‐targeted dendritic cells

et al. 2008

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Vaccine efficacy largely depends upon DC targeting and activation. The most potent TLR soluble ligands induce diffuse DC activation, which may be associated with marked pro‐inflammatory responses and possibly adverse effects. This raises the concern that effective vaccine adjuvants may similarly rely on widespread DC activation. Using a promising candidate vaccine against tuberculosis (fusion protein of Ag85B and 6‐kDa early secretory antigenic target (ESAT‐6)) formulated in the potent IC31® adjuvant, DC targeting and activation was studied in vivo, following the fate of antigen and adjuvant in the draining lymph nodes, to define the magnitude of DC targeting/activation required in vivo to induce protective vaccine responses. Unexpectedly, protective IFN‐γ‐mediated Ag85B‐ESAT‐6/IC31® responses were associated to the activation of a minute population (less than 0.3%) of CD11c+ lymph node DC, without detectable systemic pro‐inflammatory responses. This activated peripheral tissue‐derived DC population, characterized by enhanced CD80, CD86, CD40 and IL‐12p40 expression, was only identified when focusing on adjuvant‐ or antigen‐labeled CD11c+ DC, which were found to support T cell proliferation. Immunization with aluminum hydroxide adjuvant (Alum) resulted in a similar proportion of antigen‐associated DC but without detectable enhancement of CD80, CD86, CD40 or IL‐12p40 expression. Thus, potent protective IFN‐γ‐producing responses may be elicited by the exquisite activation of a minute number of in vivo targeted DC.

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Biomedical Nanotechnology Using Virus-Based Nanoparticles

Destito

Schneemann

Manchester

2009

Viruses and Nanotechnology

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CD4-Independent Protective Cytotoxic T Cells Induced in Early Life by a Non-Replicative Delivery System Based on Virus-like Particles

Cited by 18 publications

References 54 publications

Partial Activation of Neonatal CD11c+ Dendritic Cells and Induction of Adult-Like CD8+ Cytotoxic T Cell Responses by Synthetic Microspheres

Partial Activation of Neonatal CD11c+ Dendritic Cells and Induction of Adult-Like CD8+ Cytotoxic T Cell Responses by Synthetic Microspheres

Protective anti‐mycobacterial T cell responses through exquisite in vivo activation of vaccine‐targeted dendritic cells

Biomedical Nanotechnology Using Virus-Based Nanoparticles

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