Homotypic cell to cell cross-talk among human natural killer cells reveals differential and overlapping roles of 2B4 and CD2

Eun Ok Kim, Tae Jin Kim, Nayoung Kim, Sung Tae Kim, Vinay Kumar, Kyung-Mi Lee

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Human natural killer (NK) cells express an abundant level of 2B4 and CD2 on their surface. Their counter-receptors, CD48 and CD58, are also expressed on the NK cell surface, raising a question about the functional consequences of potential 2B4/ CD48 and CD2/CD58 interactions. Using blocking antibodies specific to each receptor, we demonstrated that both 2B4/ CD48 and CD2/CD58 interactions were essential for the development of NK effector functions: cytotoxicity and cytokine secretion. However, only 2B4/CD48, but not CD2/CD58, interactions were shown to be critical for the optimal NK cell proliferation in response to interleukin (IL)-2. IL-2-activated NK cells cultured in the absence of 2B4/CD48 or CD2/CD58 interactions were severely impaired for their ability to induce intracellular calcium mobilization and subsequent ERK activation upon tumor target exposure, suggesting that the early signaling pathway of NK receptors leading to impaired cytolysis and interferon (IFN)-γ secretion was inhibited. Nevertheless, these defects did not fully account for the reduced proliferation of NK cells in the absence of 2B4/CD48 interactions, because anti- CD2 or anti-CD58 monoclonal antibody (mAb)-treated NK cells, showing defective signaling and effector functions, displayed normal proliferation upon IL-2 stimulation. These results propose the signaling divergence between pathways leading to cell proliferation and cytotoxicity/cytokine release, which can be differentially regulated by 2B4 and CD2 during IL-2-driven NK cell activation. Collectively, these results reveal the importance of homotypic NK-to-NK cell cross-talk through 2B4/CD48 and CD2/CD58 pairs and further present their differential and overlapping roles in human NK cells.

Original languageEnglish
Pages (from-to)41755-41764
Number of pages10
JournalJournal of Biological Chemistry
Volume285
Issue number53
DOIs
Publication statusPublished - 2010 Dec 31
Externally publishedYes

Fingerprint

Natural Killer Cells
Interleukin-2
Cell proliferation
Cytotoxicity
Chemical activation
Cytokines
Blocking Antibodies
Interferons
Tumors
Monoclonal Antibodies
Calcium
Cell Proliferation
Defects

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Homotypic cell to cell cross-talk among human natural killer cells reveals differential and overlapping roles of 2B4 and CD2. / Kim, Eun Ok; Kim, Tae Jin; Kim, Nayoung; Kim, Sung Tae; Kumar, Vinay; Lee, Kyung-Mi.

In: Journal of Biological Chemistry, Vol. 285, No. 53, 31.12.2010, p. 41755-41764.

Research output: Contribution to journalArticle

Kim, Eun Ok ; Kim, Tae Jin ; Kim, Nayoung ; Kim, Sung Tae ; Kumar, Vinay ; Lee, Kyung-Mi. / Homotypic cell to cell cross-talk among human natural killer cells reveals differential and overlapping roles of 2B4 and CD2. In: Journal of Biological Chemistry. 2010 ; Vol. 285, No. 53. pp. 41755-41764.
@article{e4c21f3e3148425f8b4e9bede7a7a1f8,
title = "Homotypic cell to cell cross-talk among human natural killer cells reveals differential and overlapping roles of 2B4 and CD2",
abstract = "Human natural killer (NK) cells express an abundant level of 2B4 and CD2 on their surface. Their counter-receptors, CD48 and CD58, are also expressed on the NK cell surface, raising a question about the functional consequences of potential 2B4/ CD48 and CD2/CD58 interactions. Using blocking antibodies specific to each receptor, we demonstrated that both 2B4/ CD48 and CD2/CD58 interactions were essential for the development of NK effector functions: cytotoxicity and cytokine secretion. However, only 2B4/CD48, but not CD2/CD58, interactions were shown to be critical for the optimal NK cell proliferation in response to interleukin (IL)-2. IL-2-activated NK cells cultured in the absence of 2B4/CD48 or CD2/CD58 interactions were severely impaired for their ability to induce intracellular calcium mobilization and subsequent ERK activation upon tumor target exposure, suggesting that the early signaling pathway of NK receptors leading to impaired cytolysis and interferon (IFN)-γ secretion was inhibited. Nevertheless, these defects did not fully account for the reduced proliferation of NK cells in the absence of 2B4/CD48 interactions, because anti- CD2 or anti-CD58 monoclonal antibody (mAb)-treated NK cells, showing defective signaling and effector functions, displayed normal proliferation upon IL-2 stimulation. These results propose the signaling divergence between pathways leading to cell proliferation and cytotoxicity/cytokine release, which can be differentially regulated by 2B4 and CD2 during IL-2-driven NK cell activation. Collectively, these results reveal the importance of homotypic NK-to-NK cell cross-talk through 2B4/CD48 and CD2/CD58 pairs and further present their differential and overlapping roles in human NK cells.",
author = "Kim, {Eun Ok} and Kim, {Tae Jin} and Nayoung Kim and Kim, {Sung Tae} and Vinay Kumar and Kyung-Mi Lee",
year = "2010",
month = "12",
day = "31",
doi = "10.1074/jbc.M110.137976",
language = "English",
volume = "285",
pages = "41755--41764",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "53",

}

TY - JOUR

T1 - Homotypic cell to cell cross-talk among human natural killer cells reveals differential and overlapping roles of 2B4 and CD2

AU - Kim, Eun Ok

AU - Kim, Tae Jin

AU - Kim, Nayoung

AU - Kim, Sung Tae

AU - Kumar, Vinay

AU - Lee, Kyung-Mi

PY - 2010/12/31

Y1 - 2010/12/31

N2 - Human natural killer (NK) cells express an abundant level of 2B4 and CD2 on their surface. Their counter-receptors, CD48 and CD58, are also expressed on the NK cell surface, raising a question about the functional consequences of potential 2B4/ CD48 and CD2/CD58 interactions. Using blocking antibodies specific to each receptor, we demonstrated that both 2B4/ CD48 and CD2/CD58 interactions were essential for the development of NK effector functions: cytotoxicity and cytokine secretion. However, only 2B4/CD48, but not CD2/CD58, interactions were shown to be critical for the optimal NK cell proliferation in response to interleukin (IL)-2. IL-2-activated NK cells cultured in the absence of 2B4/CD48 or CD2/CD58 interactions were severely impaired for their ability to induce intracellular calcium mobilization and subsequent ERK activation upon tumor target exposure, suggesting that the early signaling pathway of NK receptors leading to impaired cytolysis and interferon (IFN)-γ secretion was inhibited. Nevertheless, these defects did not fully account for the reduced proliferation of NK cells in the absence of 2B4/CD48 interactions, because anti- CD2 or anti-CD58 monoclonal antibody (mAb)-treated NK cells, showing defective signaling and effector functions, displayed normal proliferation upon IL-2 stimulation. These results propose the signaling divergence between pathways leading to cell proliferation and cytotoxicity/cytokine release, which can be differentially regulated by 2B4 and CD2 during IL-2-driven NK cell activation. Collectively, these results reveal the importance of homotypic NK-to-NK cell cross-talk through 2B4/CD48 and CD2/CD58 pairs and further present their differential and overlapping roles in human NK cells.

AB - Human natural killer (NK) cells express an abundant level of 2B4 and CD2 on their surface. Their counter-receptors, CD48 and CD58, are also expressed on the NK cell surface, raising a question about the functional consequences of potential 2B4/ CD48 and CD2/CD58 interactions. Using blocking antibodies specific to each receptor, we demonstrated that both 2B4/ CD48 and CD2/CD58 interactions were essential for the development of NK effector functions: cytotoxicity and cytokine secretion. However, only 2B4/CD48, but not CD2/CD58, interactions were shown to be critical for the optimal NK cell proliferation in response to interleukin (IL)-2. IL-2-activated NK cells cultured in the absence of 2B4/CD48 or CD2/CD58 interactions were severely impaired for their ability to induce intracellular calcium mobilization and subsequent ERK activation upon tumor target exposure, suggesting that the early signaling pathway of NK receptors leading to impaired cytolysis and interferon (IFN)-γ secretion was inhibited. Nevertheless, these defects did not fully account for the reduced proliferation of NK cells in the absence of 2B4/CD48 interactions, because anti- CD2 or anti-CD58 monoclonal antibody (mAb)-treated NK cells, showing defective signaling and effector functions, displayed normal proliferation upon IL-2 stimulation. These results propose the signaling divergence between pathways leading to cell proliferation and cytotoxicity/cytokine release, which can be differentially regulated by 2B4 and CD2 during IL-2-driven NK cell activation. Collectively, these results reveal the importance of homotypic NK-to-NK cell cross-talk through 2B4/CD48 and CD2/CD58 pairs and further present their differential and overlapping roles in human NK cells.

UR - http://www.scopus.com/inward/record.url?scp=78650675593&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78650675593&partnerID=8YFLogxK

U2 - 10.1074/jbc.M110.137976

DO - 10.1074/jbc.M110.137976

M3 - Article

VL - 285

SP - 41755

EP - 41764

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 53

ER -