Immunogenicity of apoptotic cells in vivo: Role of antigen load, antigen-presenting cells, and cytokines

Anna Ronchetti, Patrizia Rovere, Giandomenica Iezzi, Giacomo Galati, Silvia Heltai, Maria Pia Protti, Maria Paola Garancini, Angelo A. Manfredi, Claudio Rugarli, Matteo Bellone

Research output: Contribution to journalArticle

Abstract

Apoptosis allows the clearance of unwanted cells from living tissues without causing inflammation. Processing of phagocytosed apoptotic cells yields Ags that access the cytosol and the MHC class I pathway of engulfing cells and are recognized by Ag-specific CTL. We show here that injection of apoptotic RMA cells, a syngeneic T cell lymphoma, into C57BL/6 mice results in priming of a functional and long-lasting tumor-specific immune response. Cross-priming of CTLs by apoptotic cells requires CD4+ T cell help. Apoptotic cells, however, are at least 20-fold less immunogenic than nonreplicating live cells. Immunogenicity of apoptotic cells is proportional to the number of cells injected, correlates with the serum concentration of IL-10 and IL-1α cytokines, and is enhanced in IL-10 knockout mice. Moreover, immunization with dendritic cells (DCs), but not macrophages (Mφ), pulsed with apoptotic cells primes tumor-specific CTLs and confers protection against a tumor challenge. Our findings demonstrate that tumor cells undergoing apoptosis are, though scarcely, immunogenic in vivo, outline the different roles of Mφ and DCs in the physiologic clearance of unwanted cells, and have implications in designing immunomodulating vaccines.

Original languageEnglish
Pages (from-to)130-136
Number of pages7
JournalJournal of Immunology
Volume163
Issue number1
Publication statusPublished - Jul 1 1999

Fingerprint

Antigen-Presenting Cells
Cytokines
Antigens
Interleukin-10
Dendritic Cells
Neoplasms
Cross-Priming
Apoptosis
Cytophagocytosis
T-Cell Lymphoma
Interleukin-1
Inbred C57BL Mouse
Knockout Mice
Cytosol
Immunization
Vaccines
Cell Count
Macrophages
Inflammation
T-Lymphocytes

ASJC Scopus subject areas

  • Immunology

Cite this

Immunogenicity of apoptotic cells in vivo : Role of antigen load, antigen-presenting cells, and cytokines. / Ronchetti, Anna; Rovere, Patrizia; Iezzi, Giandomenica; Galati, Giacomo; Heltai, Silvia; Protti, Maria Pia; Garancini, Maria Paola; Manfredi, Angelo A.; Rugarli, Claudio; Bellone, Matteo.

In: Journal of Immunology, Vol. 163, No. 1, 01.07.1999, p. 130-136.

Research output: Contribution to journalArticle

Ronchetti, Anna ; Rovere, Patrizia ; Iezzi, Giandomenica ; Galati, Giacomo ; Heltai, Silvia ; Protti, Maria Pia ; Garancini, Maria Paola ; Manfredi, Angelo A. ; Rugarli, Claudio ; Bellone, Matteo. / Immunogenicity of apoptotic cells in vivo : Role of antigen load, antigen-presenting cells, and cytokines. In: Journal of Immunology. 1999 ; Vol. 163, No. 1. pp. 130-136.
@article{a8c5e94701ca4de4b20bc0d250ec589c,
title = "Immunogenicity of apoptotic cells in vivo: Role of antigen load, antigen-presenting cells, and cytokines",
abstract = "Apoptosis allows the clearance of unwanted cells from living tissues without causing inflammation. Processing of phagocytosed apoptotic cells yields Ags that access the cytosol and the MHC class I pathway of engulfing cells and are recognized by Ag-specific CTL. We show here that injection of apoptotic RMA cells, a syngeneic T cell lymphoma, into C57BL/6 mice results in priming of a functional and long-lasting tumor-specific immune response. Cross-priming of CTLs by apoptotic cells requires CD4+ T cell help. Apoptotic cells, however, are at least 20-fold less immunogenic than nonreplicating live cells. Immunogenicity of apoptotic cells is proportional to the number of cells injected, correlates with the serum concentration of IL-10 and IL-1α cytokines, and is enhanced in IL-10 knockout mice. Moreover, immunization with dendritic cells (DCs), but not macrophages (Mφ), pulsed with apoptotic cells primes tumor-specific CTLs and confers protection against a tumor challenge. Our findings demonstrate that tumor cells undergoing apoptosis are, though scarcely, immunogenic in vivo, outline the different roles of Mφ and DCs in the physiologic clearance of unwanted cells, and have implications in designing immunomodulating vaccines.",
author = "Anna Ronchetti and Patrizia Rovere and Giandomenica Iezzi and Giacomo Galati and Silvia Heltai and Protti, {Maria Pia} and Garancini, {Maria Paola} and Manfredi, {Angelo A.} and Claudio Rugarli and Matteo Bellone",
year = "1999",
month = "7",
day = "1",
language = "English",
volume = "163",
pages = "130--136",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "1",

}

TY - JOUR

T1 - Immunogenicity of apoptotic cells in vivo

T2 - Role of antigen load, antigen-presenting cells, and cytokines

AU - Ronchetti, Anna

AU - Rovere, Patrizia

AU - Iezzi, Giandomenica

AU - Galati, Giacomo

AU - Heltai, Silvia

AU - Protti, Maria Pia

AU - Garancini, Maria Paola

AU - Manfredi, Angelo A.

AU - Rugarli, Claudio

AU - Bellone, Matteo

PY - 1999/7/1

Y1 - 1999/7/1

N2 - Apoptosis allows the clearance of unwanted cells from living tissues without causing inflammation. Processing of phagocytosed apoptotic cells yields Ags that access the cytosol and the MHC class I pathway of engulfing cells and are recognized by Ag-specific CTL. We show here that injection of apoptotic RMA cells, a syngeneic T cell lymphoma, into C57BL/6 mice results in priming of a functional and long-lasting tumor-specific immune response. Cross-priming of CTLs by apoptotic cells requires CD4+ T cell help. Apoptotic cells, however, are at least 20-fold less immunogenic than nonreplicating live cells. Immunogenicity of apoptotic cells is proportional to the number of cells injected, correlates with the serum concentration of IL-10 and IL-1α cytokines, and is enhanced in IL-10 knockout mice. Moreover, immunization with dendritic cells (DCs), but not macrophages (Mφ), pulsed with apoptotic cells primes tumor-specific CTLs and confers protection against a tumor challenge. Our findings demonstrate that tumor cells undergoing apoptosis are, though scarcely, immunogenic in vivo, outline the different roles of Mφ and DCs in the physiologic clearance of unwanted cells, and have implications in designing immunomodulating vaccines.

AB - Apoptosis allows the clearance of unwanted cells from living tissues without causing inflammation. Processing of phagocytosed apoptotic cells yields Ags that access the cytosol and the MHC class I pathway of engulfing cells and are recognized by Ag-specific CTL. We show here that injection of apoptotic RMA cells, a syngeneic T cell lymphoma, into C57BL/6 mice results in priming of a functional and long-lasting tumor-specific immune response. Cross-priming of CTLs by apoptotic cells requires CD4+ T cell help. Apoptotic cells, however, are at least 20-fold less immunogenic than nonreplicating live cells. Immunogenicity of apoptotic cells is proportional to the number of cells injected, correlates with the serum concentration of IL-10 and IL-1α cytokines, and is enhanced in IL-10 knockout mice. Moreover, immunization with dendritic cells (DCs), but not macrophages (Mφ), pulsed with apoptotic cells primes tumor-specific CTLs and confers protection against a tumor challenge. Our findings demonstrate that tumor cells undergoing apoptosis are, though scarcely, immunogenic in vivo, outline the different roles of Mφ and DCs in the physiologic clearance of unwanted cells, and have implications in designing immunomodulating vaccines.

UR - http://www.scopus.com/inward/record.url?scp=0033168145&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033168145&partnerID=8YFLogxK

M3 - Article

C2 - 10384108

AN - SCOPUS:0033168145

VL - 163

SP - 130

EP - 136

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 1

ER -