Dendritic Cells Matured by Inflammation Induce CD86-Dependent Priming of Naive CD8(+) T Cells in the Absence of Their Cognate Peptide Antigen

Asher Maroof; Lynette Beattie; Alun Kirby; Mark Coles; Paul M. Kaye

doi:10.4049/jimmunol.0901330

Dendritic Cells Matured by Inflammation Induce CD86-Dependent Priming of Naive CD8(+) T Cells in the Absence of Their Cognate Peptide Antigen

Asher Maroof, Lynette Beattie, Alun Kirby, Mark Coles, Paul M. Kaye

Research output: Contribution to journal › Article › peer-review

Abstract

Dendritic cells (DC) licensed by the interaction between pathogen products and pattern recognition receptors can activate naive T cells to undergo Ag-dependent proliferation and cytokine production. In contrast, DC induced to mature by trans-acting inflammatory stimuli are believed to only be capable of supporting Ag-dependent proliferative responses. In this study, we show that uninfected DC matured as a consequence of Leishmania-induced inflammation induce CD8(+) T cells to proliferate in the absence of their cognate Ag. We separated splenic DC from Leishmania donovani-infected mice into those that contained parasites and had been activated to induce IL-12p40, from those that had undergone only partial maturation, measured by increased CD86 expression in the absence of IL-12p40 induction. We then showed that these partially matured DC could induce exogenous peptide-independent proliferation of OT-I and F5 CD8(+) TCR transgenic T cells, as well as polyclonal CD8(+) T cells. Proliferation of OT-I cells was significantly inhibited in vitro and in vivo by anti-CD86 mAb but not by anti-CD80 mAb and could also be inhibited by cyclosporine A. Proliferating OT-I cells did not produce IFN-gamma, even when re-exposed to mature DC. However, these primed OT-I cells subsequently produced effector cytokines, not Just on exposure to their cognate peptide but, more importantly, to weak exogenous TCR agonists that otherwise failed to induce IFN-gamma. We further showed that OT-I cells undergoing locally driven proliferation to another pathogen, Streptococcus pneumoniae, rapidly seeded other lymphoid tissues, suggesting that CD8(+) T cells primed in this way may play a role in rapidly countering pathogen dissemination.

Original language	English
Pages (from-to)	7095-7103
Number of pages	9
Journal	Journal of Immunology
Volume	183
Issue number	11
DOIs	https://doi.org/10.4049/jimmunol.0901330
Publication status	Published - 1 Dec 2009

Keywords

LEISHMANIA-DONOVANI INFECTION
INNATE IMMUNE-SYSTEM
BYSTANDER ACTIVATION
ADAPTIVE IMMUNITY
CUTTING EDGE
LYMPHOCYTES
MATURATION
EXPANSION
MODEL
SELF

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10.4049/jimmunol.0901330

http://www.jimmunol.org/content/183/11/7095

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@article{60f794bd5e6d45459c0eee38021f0388,

title = "Dendritic Cells Matured by Inflammation Induce CD86-Dependent Priming of Naive CD8(+) T Cells in the Absence of Their Cognate Peptide Antigen",

abstract = "Dendritic cells (DC) licensed by the interaction between pathogen products and pattern recognition receptors can activate naive T cells to undergo Ag-dependent proliferation and cytokine production. In contrast, DC induced to mature by trans-acting inflammatory stimuli are believed to only be capable of supporting Ag-dependent proliferative responses. In this study, we show that uninfected DC matured as a consequence of Leishmania-induced inflammation induce CD8(+) T cells to proliferate in the absence of their cognate Ag. We separated splenic DC from Leishmania donovani-infected mice into those that contained parasites and had been activated to induce IL-12p40, from those that had undergone only partial maturation, measured by increased CD86 expression in the absence of IL-12p40 induction. We then showed that these partially matured DC could induce exogenous peptide-independent proliferation of OT-I and F5 CD8(+) TCR transgenic T cells, as well as polyclonal CD8(+) T cells. Proliferation of OT-I cells was significantly inhibited in vitro and in vivo by anti-CD86 mAb but not by anti-CD80 mAb and could also be inhibited by cyclosporine A. Proliferating OT-I cells did not produce IFN-gamma, even when re-exposed to mature DC. However, these primed OT-I cells subsequently produced effector cytokines, not Just on exposure to their cognate peptide but, more importantly, to weak exogenous TCR agonists that otherwise failed to induce IFN-gamma. We further showed that OT-I cells undergoing locally driven proliferation to another pathogen, Streptococcus pneumoniae, rapidly seeded other lymphoid tissues, suggesting that CD8(+) T cells primed in this way may play a role in rapidly countering pathogen dissemination. ",

keywords = "LEISHMANIA-DONOVANI INFECTION, INNATE IMMUNE-SYSTEM, BYSTANDER ACTIVATION, ADAPTIVE IMMUNITY, CUTTING EDGE, LYMPHOCYTES, MATURATION, EXPANSION, MODEL, SELF",

author = "Asher Maroof and Lynette Beattie and Alun Kirby and Mark Coles and Kaye, {Paul M.}",

year = "2009",

month = dec,

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doi = "10.4049/jimmunol.0901330",

language = "English",

volume = "183",

pages = "7095--7103",

journal = "Journal of Immunology",

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publisher = "American Association of Immunologists",

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T1 - Dendritic Cells Matured by Inflammation Induce CD86-Dependent Priming of Naive CD8(+) T Cells in the Absence of Their Cognate Peptide Antigen

AU - Maroof, Asher

AU - Beattie, Lynette

AU - Kirby, Alun

AU - Coles, Mark

AU - Kaye, Paul M.

PY - 2009/12/1

Y1 - 2009/12/1

N2 - Dendritic cells (DC) licensed by the interaction between pathogen products and pattern recognition receptors can activate naive T cells to undergo Ag-dependent proliferation and cytokine production. In contrast, DC induced to mature by trans-acting inflammatory stimuli are believed to only be capable of supporting Ag-dependent proliferative responses. In this study, we show that uninfected DC matured as a consequence of Leishmania-induced inflammation induce CD8(+) T cells to proliferate in the absence of their cognate Ag. We separated splenic DC from Leishmania donovani-infected mice into those that contained parasites and had been activated to induce IL-12p40, from those that had undergone only partial maturation, measured by increased CD86 expression in the absence of IL-12p40 induction. We then showed that these partially matured DC could induce exogenous peptide-independent proliferation of OT-I and F5 CD8(+) TCR transgenic T cells, as well as polyclonal CD8(+) T cells. Proliferation of OT-I cells was significantly inhibited in vitro and in vivo by anti-CD86 mAb but not by anti-CD80 mAb and could also be inhibited by cyclosporine A. Proliferating OT-I cells did not produce IFN-gamma, even when re-exposed to mature DC. However, these primed OT-I cells subsequently produced effector cytokines, not Just on exposure to their cognate peptide but, more importantly, to weak exogenous TCR agonists that otherwise failed to induce IFN-gamma. We further showed that OT-I cells undergoing locally driven proliferation to another pathogen, Streptococcus pneumoniae, rapidly seeded other lymphoid tissues, suggesting that CD8(+) T cells primed in this way may play a role in rapidly countering pathogen dissemination.

AB - Dendritic cells (DC) licensed by the interaction between pathogen products and pattern recognition receptors can activate naive T cells to undergo Ag-dependent proliferation and cytokine production. In contrast, DC induced to mature by trans-acting inflammatory stimuli are believed to only be capable of supporting Ag-dependent proliferative responses. In this study, we show that uninfected DC matured as a consequence of Leishmania-induced inflammation induce CD8(+) T cells to proliferate in the absence of their cognate Ag. We separated splenic DC from Leishmania donovani-infected mice into those that contained parasites and had been activated to induce IL-12p40, from those that had undergone only partial maturation, measured by increased CD86 expression in the absence of IL-12p40 induction. We then showed that these partially matured DC could induce exogenous peptide-independent proliferation of OT-I and F5 CD8(+) TCR transgenic T cells, as well as polyclonal CD8(+) T cells. Proliferation of OT-I cells was significantly inhibited in vitro and in vivo by anti-CD86 mAb but not by anti-CD80 mAb and could also be inhibited by cyclosporine A. Proliferating OT-I cells did not produce IFN-gamma, even when re-exposed to mature DC. However, these primed OT-I cells subsequently produced effector cytokines, not Just on exposure to their cognate peptide but, more importantly, to weak exogenous TCR agonists that otherwise failed to induce IFN-gamma. We further showed that OT-I cells undergoing locally driven proliferation to another pathogen, Streptococcus pneumoniae, rapidly seeded other lymphoid tissues, suggesting that CD8(+) T cells primed in this way may play a role in rapidly countering pathogen dissemination.

KW - LEISHMANIA-DONOVANI INFECTION

KW - INNATE IMMUNE-SYSTEM

KW - BYSTANDER ACTIVATION

KW - ADAPTIVE IMMUNITY

KW - CUTTING EDGE

KW - LYMPHOCYTES

KW - MATURATION

KW - EXPANSION

KW - MODEL

KW - SELF

UR - http://www.scopus.com/inward/record.url?scp=73349099041&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.0901330

DO - 10.4049/jimmunol.0901330

M3 - Article

C2 - 19917700

SN - 0022-1767

VL - 183

SP - 7095

EP - 7103

JO - Journal of Immunology

JF - Journal of Immunology

IS - 11

ER -

Dendritic Cells Matured by Inflammation Induce CD86-Dependent Priming of Naive CD8(+) T Cells in the Absence of Their Cognate Peptide Antigen

Abstract

Keywords

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