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In vivo triggering through 4-1BB enables Th-independent priming of CTL in the presence of an intact CD28 costimulatory pathway

Standard

In vivo triggering through 4-1BB enables Th-independent priming of CTL in the presence of an intact CD28 costimulatory pathway. / Diehl, Linda; van Mierlo, Geertje J D; den Boer, Annemieke T; van der Voort, Ellen; Fransen, Marieke; van Bostelen, Liesbeth; Krimpenfort, Paul; Melief, Cornelis J M; Mittler, Robert; Toes, Rene E M; Offringa, Rienk.

in: J IMMUNOL, Jahrgang 168, Nr. 8, 15.04.2002, S. 3755-62.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Diehl, L, van Mierlo, GJD, den Boer, AT, van der Voort, E, Fransen, M, van Bostelen, L, Krimpenfort, P, Melief, CJM, Mittler, R, Toes, REM & Offringa, R 2002, 'In vivo triggering through 4-1BB enables Th-independent priming of CTL in the presence of an intact CD28 costimulatory pathway', J IMMUNOL, Jg. 168, Nr. 8, S. 3755-62.

APA

Diehl, L., van Mierlo, G. J. D., den Boer, A. T., van der Voort, E., Fransen, M., van Bostelen, L., Krimpenfort, P., Melief, C. J. M., Mittler, R., Toes, R. E. M., & Offringa, R. (2002). In vivo triggering through 4-1BB enables Th-independent priming of CTL in the presence of an intact CD28 costimulatory pathway. J IMMUNOL, 168(8), 3755-62.

Vancouver

Diehl L, van Mierlo GJD, den Boer AT, van der Voort E, Fransen M, van Bostelen L et al. In vivo triggering through 4-1BB enables Th-independent priming of CTL in the presence of an intact CD28 costimulatory pathway. J IMMUNOL. 2002 Apr 15;168(8):3755-62.

Bibtex

@article{83a9d8f7ef60462991e1e1de5b195679,
title = "In vivo triggering through 4-1BB enables Th-independent priming of CTL in the presence of an intact CD28 costimulatory pathway",
abstract = "Triggering of 4-1BB, a member of the TNFR family, through in vivo administration of agonistic anti-4-1BB Ab delivers a powerful costimulatory signal to CTL. We found this signal to effectively replace the need for CD4(+) T cell help in the cross-priming of tumor-specific CTL immunity. Furthermore, 4-1BB Ab can convert an otherwise tolerogenic peptide vaccine into a formulation capable of efficient CTL priming. Initial activation of naive CTL can occur in the absence of 4-1BB costimulation, but this signal permits increased survival of Ag-stimulated CTL. Because naive CTL do not express 4-1BB at their surface, susceptibility to 4-1BB triggering depends on prior up-regulation of this receptor. We show that this requires both stimulation of the TCR and CD28-dependent costimulation. Accordingly, blockade of the CD28-costimulatory pathway abrogates the capacity of agonistic anti-4-1BB Ab to trigger Th-independent CTL immunity. In conclusion, our data reveal that the 4-1BB-mediated survival signal is positioned downstream of Ag-specific TCR triggering and CD28-dependent costimulation of naive CTL. The powerful effects of 4-1BB triggering on the induction, amplification, and persistence of CTL responses provide a novel strategy for increasing the potency of vaccines against cancers.",
keywords = "4-1BB Ligand, Animals, Antigens, CD, Antigens, CD137, Antigens, CD28, CD4-Positive T-Lymphocytes, Cell Survival, Cells, Cultured, Cytotoxicity, Immunologic, Dendritic Cells, Immune Sera, Injections, Intraperitoneal, Injections, Intravenous, Interphase, Ligands, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Receptors, Nerve Growth Factor, Receptors, Tumor Necrosis Factor, Signal Transduction, T-Lymphocytes, Cytotoxic, Tumor Necrosis Factor-alpha",
author = "Linda Diehl and {van Mierlo}, {Geertje J D} and {den Boer}, {Annemieke T} and {van der Voort}, Ellen and Marieke Fransen and {van Bostelen}, Liesbeth and Paul Krimpenfort and Melief, {Cornelis J M} and Robert Mittler and Toes, {Rene E M} and Rienk Offringa",
year = "2002",
month = apr,
day = "15",
language = "English",
volume = "168",
pages = "3755--62",
journal = "J IMMUNOL",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "8",

}

RIS

TY - JOUR

T1 - In vivo triggering through 4-1BB enables Th-independent priming of CTL in the presence of an intact CD28 costimulatory pathway

AU - Diehl, Linda

AU - van Mierlo, Geertje J D

AU - den Boer, Annemieke T

AU - van der Voort, Ellen

AU - Fransen, Marieke

AU - van Bostelen, Liesbeth

AU - Krimpenfort, Paul

AU - Melief, Cornelis J M

AU - Mittler, Robert

AU - Toes, Rene E M

AU - Offringa, Rienk

PY - 2002/4/15

Y1 - 2002/4/15

N2 - Triggering of 4-1BB, a member of the TNFR family, through in vivo administration of agonistic anti-4-1BB Ab delivers a powerful costimulatory signal to CTL. We found this signal to effectively replace the need for CD4(+) T cell help in the cross-priming of tumor-specific CTL immunity. Furthermore, 4-1BB Ab can convert an otherwise tolerogenic peptide vaccine into a formulation capable of efficient CTL priming. Initial activation of naive CTL can occur in the absence of 4-1BB costimulation, but this signal permits increased survival of Ag-stimulated CTL. Because naive CTL do not express 4-1BB at their surface, susceptibility to 4-1BB triggering depends on prior up-regulation of this receptor. We show that this requires both stimulation of the TCR and CD28-dependent costimulation. Accordingly, blockade of the CD28-costimulatory pathway abrogates the capacity of agonistic anti-4-1BB Ab to trigger Th-independent CTL immunity. In conclusion, our data reveal that the 4-1BB-mediated survival signal is positioned downstream of Ag-specific TCR triggering and CD28-dependent costimulation of naive CTL. The powerful effects of 4-1BB triggering on the induction, amplification, and persistence of CTL responses provide a novel strategy for increasing the potency of vaccines against cancers.

AB - Triggering of 4-1BB, a member of the TNFR family, through in vivo administration of agonistic anti-4-1BB Ab delivers a powerful costimulatory signal to CTL. We found this signal to effectively replace the need for CD4(+) T cell help in the cross-priming of tumor-specific CTL immunity. Furthermore, 4-1BB Ab can convert an otherwise tolerogenic peptide vaccine into a formulation capable of efficient CTL priming. Initial activation of naive CTL can occur in the absence of 4-1BB costimulation, but this signal permits increased survival of Ag-stimulated CTL. Because naive CTL do not express 4-1BB at their surface, susceptibility to 4-1BB triggering depends on prior up-regulation of this receptor. We show that this requires both stimulation of the TCR and CD28-dependent costimulation. Accordingly, blockade of the CD28-costimulatory pathway abrogates the capacity of agonistic anti-4-1BB Ab to trigger Th-independent CTL immunity. In conclusion, our data reveal that the 4-1BB-mediated survival signal is positioned downstream of Ag-specific TCR triggering and CD28-dependent costimulation of naive CTL. The powerful effects of 4-1BB triggering on the induction, amplification, and persistence of CTL responses provide a novel strategy for increasing the potency of vaccines against cancers.

KW - 4-1BB Ligand

KW - Animals

KW - Antigens, CD

KW - Antigens, CD137

KW - Antigens, CD28

KW - CD4-Positive T-Lymphocytes

KW - Cell Survival

KW - Cells, Cultured

KW - Cytotoxicity, Immunologic

KW - Dendritic Cells

KW - Immune Sera

KW - Injections, Intraperitoneal

KW - Injections, Intravenous

KW - Interphase

KW - Ligands

KW - Lymphocyte Activation

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Mice, Transgenic

KW - Receptors, Nerve Growth Factor

KW - Receptors, Tumor Necrosis Factor

KW - Signal Transduction

KW - T-Lymphocytes, Cytotoxic

KW - Tumor Necrosis Factor-alpha

M3 - SCORING: Journal article

C2 - 11937526

VL - 168

SP - 3755

EP - 3762

JO - J IMMUNOL

JF - J IMMUNOL

SN - 0022-1767

IS - 8

ER -