Perforin is required for innate and adaptive immunity induced by heat shock protein gp96

Natasa Strbo, Satoshi Oizumi, Vlatka Sotosek-Tokmadzic, Eckhard R. Podack

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Tumor-secreted gp96-Ig is highly immunogenic and triggers CD8 T cell-mediated tumor rejection. In vivo secreted gp96-Ig and gp96-myc cause NK activation and clonal expansion of specific CD8+ CTL in wild-type and in Fas-ligand-deficient (gld) mice but not in perforin- (PKO) or IFN-γ-deficient (GKO) mice. Transfer of perforin-competent NK cells restores the ability of PKO mice to clonally expand CD8 CTL in response to gp96-Ig. The data demonstrate an essential role for perforin-mediated functions in the activation of innate and adaptive immunity by heat shock protein gp96-peptide complexes. Crosspresentation of antigens by heat shock proteins seems to require a perforin-dependent positive feedback loop between NK and DC for both sustained NK activation and clonal CTL expansion. The studies also explain how depressed NK activity in patients with tumors or after viral infections could diminish CTL responses.

Original languageEnglish
Pages (from-to)381-390
Number of pages10
JournalImmunity
Volume18
Issue number3
DOIs
StatePublished - Mar 1 2003

Fingerprint

Perforin
Adaptive Immunity
Heat-Shock Proteins
Innate Immunity
Neoplasms
Fas Ligand Protein
Virus Diseases
Natural Killer Cells
T-Lymphocytes
Antigens
Peptides

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

Perforin is required for innate and adaptive immunity induced by heat shock protein gp96. / Strbo, Natasa; Oizumi, Satoshi; Sotosek-Tokmadzic, Vlatka; Podack, Eckhard R.

In: Immunity, Vol. 18, No. 3, 01.03.2003, p. 381-390.

Research output: Contribution to journalArticle

Strbo, Natasa ; Oizumi, Satoshi ; Sotosek-Tokmadzic, Vlatka ; Podack, Eckhard R. / Perforin is required for innate and adaptive immunity induced by heat shock protein gp96. In: Immunity. 2003 ; Vol. 18, No. 3. pp. 381-390.
@article{439a2f8b99664684ab20785f2b565627,
title = "Perforin is required for innate and adaptive immunity induced by heat shock protein gp96",
abstract = "Tumor-secreted gp96-Ig is highly immunogenic and triggers CD8 T cell-mediated tumor rejection. In vivo secreted gp96-Ig and gp96-myc cause NK activation and clonal expansion of specific CD8+ CTL in wild-type and in Fas-ligand-deficient (gld) mice but not in perforin- (PKO) or IFN-γ-deficient (GKO) mice. Transfer of perforin-competent NK cells restores the ability of PKO mice to clonally expand CD8 CTL in response to gp96-Ig. The data demonstrate an essential role for perforin-mediated functions in the activation of innate and adaptive immunity by heat shock protein gp96-peptide complexes. Crosspresentation of antigens by heat shock proteins seems to require a perforin-dependent positive feedback loop between NK and DC for both sustained NK activation and clonal CTL expansion. The studies also explain how depressed NK activity in patients with tumors or after viral infections could diminish CTL responses.",
author = "Natasa Strbo and Satoshi Oizumi and Vlatka Sotosek-Tokmadzic and Podack, {Eckhard R.}",
year = "2003",
month = "3",
day = "1",
doi = "10.1016/S1074-7613(03)00056-6",
language = "English",
volume = "18",
pages = "381--390",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "3",

}

TY - JOUR

T1 - Perforin is required for innate and adaptive immunity induced by heat shock protein gp96

AU - Strbo, Natasa

AU - Oizumi, Satoshi

AU - Sotosek-Tokmadzic, Vlatka

AU - Podack, Eckhard R.

PY - 2003/3/1

Y1 - 2003/3/1

N2 - Tumor-secreted gp96-Ig is highly immunogenic and triggers CD8 T cell-mediated tumor rejection. In vivo secreted gp96-Ig and gp96-myc cause NK activation and clonal expansion of specific CD8+ CTL in wild-type and in Fas-ligand-deficient (gld) mice but not in perforin- (PKO) or IFN-γ-deficient (GKO) mice. Transfer of perforin-competent NK cells restores the ability of PKO mice to clonally expand CD8 CTL in response to gp96-Ig. The data demonstrate an essential role for perforin-mediated functions in the activation of innate and adaptive immunity by heat shock protein gp96-peptide complexes. Crosspresentation of antigens by heat shock proteins seems to require a perforin-dependent positive feedback loop between NK and DC for both sustained NK activation and clonal CTL expansion. The studies also explain how depressed NK activity in patients with tumors or after viral infections could diminish CTL responses.

AB - Tumor-secreted gp96-Ig is highly immunogenic and triggers CD8 T cell-mediated tumor rejection. In vivo secreted gp96-Ig and gp96-myc cause NK activation and clonal expansion of specific CD8+ CTL in wild-type and in Fas-ligand-deficient (gld) mice but not in perforin- (PKO) or IFN-γ-deficient (GKO) mice. Transfer of perforin-competent NK cells restores the ability of PKO mice to clonally expand CD8 CTL in response to gp96-Ig. The data demonstrate an essential role for perforin-mediated functions in the activation of innate and adaptive immunity by heat shock protein gp96-peptide complexes. Crosspresentation of antigens by heat shock proteins seems to require a perforin-dependent positive feedback loop between NK and DC for both sustained NK activation and clonal CTL expansion. The studies also explain how depressed NK activity in patients with tumors or after viral infections could diminish CTL responses.

UR - http://www.scopus.com/inward/record.url?scp=0037343184&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037343184&partnerID=8YFLogxK

U2 - 10.1016/S1074-7613(03)00056-6

DO - 10.1016/S1074-7613(03)00056-6

M3 - Article

C2 - 12648455

AN - SCOPUS:0037343184

VL - 18

SP - 381

EP - 390

JO - Immunity

JF - Immunity

SN - 1074-7613

IS - 3

ER -