Interleukin 2 and interleukin 15 differentially predispose natural killer cells to apoptosis mediated by endothelial and tumour cells

Luigi Rodella, Loris Zamai, Rita Rezzani, Marco Artico, Giovanni Peri, Mirella Falconi, Andrea Facchini, Giuseppe Pelusi, Marco Vitale

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Human natural killer (NK) cells constitutively express the β- and γ-chains of the interleukin 2 (IL-2)/IL-15 receptor, and both IL-2 and IL-15 are able to activate NK cell proliferation and cytotoxicity. When IL-2-primed human NK cells are exposed to sensitive targets (i.e. K562) they undergo apoptosis mediated by the γ2-integrin CD18. Here, we demonstrate that: (i) endothelial cells, similar to K562 tumour target cells, induce apoptosis of IL-2-primed NK cells; (ii) endothelial- and K562 cell-induced apoptosis is significantly lower in IL-15 than in IL-2-stimulated NK cells; (iii) a critical role in the apoptosis of IL-2-primed NK cells is played by the α-chain of the IL-2 receptor. Our data show for the first time that IL-2-activated NK cells can die by apoptosis upon contact with the vascular endothelium, which is a necessary step for their extravasation, with a direct pathophysiological relevance on the strategy of adoptive immunotherapy of cancer. On the other hand, IL-15, although generating a similar level of activation of NK cells, largely prevents their apoptotic fate. Therefore, IL-15 produced early in the immune response, when T cells are not yet activated, generates lymphokine-activated killer cells that are efficient killers relatively protected from apoptosis. Once activated, T cells produce IL-2 that overcomes the effect of IL-15 on NK cells, paving the way for their death by apoptosis.

Original languageEnglish
Pages (from-to)442-450
Number of pages9
JournalBritish Journal of Haematology
Volume115
Issue number2
DOIs
Publication statusPublished - 2001

Fingerprint

Interleukin-15
Natural Killer Cells
Interleukin-2
Endothelial Cells
Apoptosis
Neoplasms
Interleukin-15 Receptors
T-Lymphocytes
Adoptive Immunotherapy
Lymphokine-Activated Killer Cells
K562 Cells
Interleukin-2 Receptors
Vascular Endothelium
Integrins
Cell Proliferation

Keywords

  • Adoptive immunotherapy
  • Apoptosis
  • Cytokines
  • Endothelium
  • NK cells

ASJC Scopus subject areas

  • Hematology

Cite this

Interleukin 2 and interleukin 15 differentially predispose natural killer cells to apoptosis mediated by endothelial and tumour cells. / Rodella, Luigi; Zamai, Loris; Rezzani, Rita; Artico, Marco; Peri, Giovanni; Falconi, Mirella; Facchini, Andrea; Pelusi, Giuseppe; Vitale, Marco.

In: British Journal of Haematology, Vol. 115, No. 2, 2001, p. 442-450.

Research output: Contribution to journalArticle

Rodella, L, Zamai, L, Rezzani, R, Artico, M, Peri, G, Falconi, M, Facchini, A, Pelusi, G & Vitale, M 2001, 'Interleukin 2 and interleukin 15 differentially predispose natural killer cells to apoptosis mediated by endothelial and tumour cells', British Journal of Haematology, vol. 115, no. 2, pp. 442-450. https://doi.org/10.1046/j.1365-2141.2001.03055.x
Rodella, Luigi ; Zamai, Loris ; Rezzani, Rita ; Artico, Marco ; Peri, Giovanni ; Falconi, Mirella ; Facchini, Andrea ; Pelusi, Giuseppe ; Vitale, Marco. / Interleukin 2 and interleukin 15 differentially predispose natural killer cells to apoptosis mediated by endothelial and tumour cells. In: British Journal of Haematology. 2001 ; Vol. 115, No. 2. pp. 442-450.
@article{fe0fcf26e12149f98cddf09b2dd428f6,
title = "Interleukin 2 and interleukin 15 differentially predispose natural killer cells to apoptosis mediated by endothelial and tumour cells",
abstract = "Human natural killer (NK) cells constitutively express the β- and γ-chains of the interleukin 2 (IL-2)/IL-15 receptor, and both IL-2 and IL-15 are able to activate NK cell proliferation and cytotoxicity. When IL-2-primed human NK cells are exposed to sensitive targets (i.e. K562) they undergo apoptosis mediated by the γ2-integrin CD18. Here, we demonstrate that: (i) endothelial cells, similar to K562 tumour target cells, induce apoptosis of IL-2-primed NK cells; (ii) endothelial- and K562 cell-induced apoptosis is significantly lower in IL-15 than in IL-2-stimulated NK cells; (iii) a critical role in the apoptosis of IL-2-primed NK cells is played by the α-chain of the IL-2 receptor. Our data show for the first time that IL-2-activated NK cells can die by apoptosis upon contact with the vascular endothelium, which is a necessary step for their extravasation, with a direct pathophysiological relevance on the strategy of adoptive immunotherapy of cancer. On the other hand, IL-15, although generating a similar level of activation of NK cells, largely prevents their apoptotic fate. Therefore, IL-15 produced early in the immune response, when T cells are not yet activated, generates lymphokine-activated killer cells that are efficient killers relatively protected from apoptosis. Once activated, T cells produce IL-2 that overcomes the effect of IL-15 on NK cells, paving the way for their death by apoptosis.",
keywords = "Adoptive immunotherapy, Apoptosis, Cytokines, Endothelium, NK cells",
author = "Luigi Rodella and Loris Zamai and Rita Rezzani and Marco Artico and Giovanni Peri and Mirella Falconi and Andrea Facchini and Giuseppe Pelusi and Marco Vitale",
year = "2001",
doi = "10.1046/j.1365-2141.2001.03055.x",
language = "English",
volume = "115",
pages = "442--450",
journal = "British Journal of Haematology",
issn = "0007-1048",
publisher = "John Wiley & Sons, Ltd (10.1111)",
number = "2",

}

TY - JOUR

T1 - Interleukin 2 and interleukin 15 differentially predispose natural killer cells to apoptosis mediated by endothelial and tumour cells

AU - Rodella, Luigi

AU - Zamai, Loris

AU - Rezzani, Rita

AU - Artico, Marco

AU - Peri, Giovanni

AU - Falconi, Mirella

AU - Facchini, Andrea

AU - Pelusi, Giuseppe

AU - Vitale, Marco

PY - 2001

Y1 - 2001

N2 - Human natural killer (NK) cells constitutively express the β- and γ-chains of the interleukin 2 (IL-2)/IL-15 receptor, and both IL-2 and IL-15 are able to activate NK cell proliferation and cytotoxicity. When IL-2-primed human NK cells are exposed to sensitive targets (i.e. K562) they undergo apoptosis mediated by the γ2-integrin CD18. Here, we demonstrate that: (i) endothelial cells, similar to K562 tumour target cells, induce apoptosis of IL-2-primed NK cells; (ii) endothelial- and K562 cell-induced apoptosis is significantly lower in IL-15 than in IL-2-stimulated NK cells; (iii) a critical role in the apoptosis of IL-2-primed NK cells is played by the α-chain of the IL-2 receptor. Our data show for the first time that IL-2-activated NK cells can die by apoptosis upon contact with the vascular endothelium, which is a necessary step for their extravasation, with a direct pathophysiological relevance on the strategy of adoptive immunotherapy of cancer. On the other hand, IL-15, although generating a similar level of activation of NK cells, largely prevents their apoptotic fate. Therefore, IL-15 produced early in the immune response, when T cells are not yet activated, generates lymphokine-activated killer cells that are efficient killers relatively protected from apoptosis. Once activated, T cells produce IL-2 that overcomes the effect of IL-15 on NK cells, paving the way for their death by apoptosis.

AB - Human natural killer (NK) cells constitutively express the β- and γ-chains of the interleukin 2 (IL-2)/IL-15 receptor, and both IL-2 and IL-15 are able to activate NK cell proliferation and cytotoxicity. When IL-2-primed human NK cells are exposed to sensitive targets (i.e. K562) they undergo apoptosis mediated by the γ2-integrin CD18. Here, we demonstrate that: (i) endothelial cells, similar to K562 tumour target cells, induce apoptosis of IL-2-primed NK cells; (ii) endothelial- and K562 cell-induced apoptosis is significantly lower in IL-15 than in IL-2-stimulated NK cells; (iii) a critical role in the apoptosis of IL-2-primed NK cells is played by the α-chain of the IL-2 receptor. Our data show for the first time that IL-2-activated NK cells can die by apoptosis upon contact with the vascular endothelium, which is a necessary step for their extravasation, with a direct pathophysiological relevance on the strategy of adoptive immunotherapy of cancer. On the other hand, IL-15, although generating a similar level of activation of NK cells, largely prevents their apoptotic fate. Therefore, IL-15 produced early in the immune response, when T cells are not yet activated, generates lymphokine-activated killer cells that are efficient killers relatively protected from apoptosis. Once activated, T cells produce IL-2 that overcomes the effect of IL-15 on NK cells, paving the way for their death by apoptosis.

KW - Adoptive immunotherapy

KW - Apoptosis

KW - Cytokines

KW - Endothelium

KW - NK cells

UR - http://www.scopus.com/inward/record.url?scp=0035723884&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035723884&partnerID=8YFLogxK

U2 - 10.1046/j.1365-2141.2001.03055.x

DO - 10.1046/j.1365-2141.2001.03055.x

M3 - Article

C2 - 11703348

AN - SCOPUS:0035723884

VL - 115

SP - 442

EP - 450

JO - British Journal of Haematology

JF - British Journal of Haematology

SN - 0007-1048

IS - 2

ER -