Co-stimulation of T cells results in distinct IL-10 and TNF-alpha cytokine profiles dependent on binding to ICAM-1, ICAM-2 or ICAM-3

D A Bleijs, R de Waal-Malefyt, C G Figdor, Y van Kooyk

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The LFA-1 adhesion molecule is involved in cell adhesion events of leukocytes through binding to ICAM-1, ICAM-2 and ICAM-3. Whether binding to either of these ligands similarly affects co-stimulation of T cells and cytokine secretion is unknown. We demonstrated that LFA-1 co-stimulation under suboptimal concentrations of anti-CD3 monoclonal antibodies resulted in high, intermediate and weak proliferation of T cells on ICAM-1, -2, and -3, respectively, which correlates with the distinct affinities of LFA-1 for these ligands. Furthermore, we investigated whether binding to ICAM-1, -2 or -3 induced different cytokine profiles, thus regulating T helper cell function. Granulocyte-macrophage colony-stimulating factor and IFN-gamma were secreted in high amounts, whereas IL-2, IL-4 and IL-5 could not be detected. Interestingly, we observed that LFA-1/ICAM-1 co-stimulation of T cells resulted in high production of the Th2 cytokine IL-10 compared to ICAM-2 or ICAM-3 co-stimulation. In contrast, ICAM-2 and ICAM-3 induced a much stronger secretion of the Th1 cytokine TNF-alpha compared to LFA-1/ICAM-1 induced co-stimulation, despite the lower proliferation rate. These results demonstrate that besides facilitating cell adhesion, LFA-1 serves as a potent co-stimulatory molecule by inducing different cytokine patterns depending on the ligand bound.

Original languageEnglish
Pages (from-to)2248-58
Number of pages11
JournalEuropean Journal of Immunology
Volume29
Issue number7
DOIs
Publication statusPublished - Jul 1999

Cite this

@article{f2d89d718693495696a49da52395564f,
title = "Co-stimulation of T cells results in distinct IL-10 and TNF-alpha cytokine profiles dependent on binding to ICAM-1, ICAM-2 or ICAM-3",
abstract = "The LFA-1 adhesion molecule is involved in cell adhesion events of leukocytes through binding to ICAM-1, ICAM-2 and ICAM-3. Whether binding to either of these ligands similarly affects co-stimulation of T cells and cytokine secretion is unknown. We demonstrated that LFA-1 co-stimulation under suboptimal concentrations of anti-CD3 monoclonal antibodies resulted in high, intermediate and weak proliferation of T cells on ICAM-1, -2, and -3, respectively, which correlates with the distinct affinities of LFA-1 for these ligands. Furthermore, we investigated whether binding to ICAM-1, -2 or -3 induced different cytokine profiles, thus regulating T helper cell function. Granulocyte-macrophage colony-stimulating factor and IFN-gamma were secreted in high amounts, whereas IL-2, IL-4 and IL-5 could not be detected. Interestingly, we observed that LFA-1/ICAM-1 co-stimulation of T cells resulted in high production of the Th2 cytokine IL-10 compared to ICAM-2 or ICAM-3 co-stimulation. In contrast, ICAM-2 and ICAM-3 induced a much stronger secretion of the Th1 cytokine TNF-alpha compared to LFA-1/ICAM-1 induced co-stimulation, despite the lower proliferation rate. These results demonstrate that besides facilitating cell adhesion, LFA-1 serves as a potent co-stimulatory molecule by inducing different cytokine patterns depending on the ligand bound.",
keywords = "Antigens, CD/metabolism, Antigens, Differentiation, Cell Adhesion, Cell Adhesion Molecules/metabolism, Humans, In Vitro Techniques, Intercellular Adhesion Molecule-1/metabolism, Interleukin-10/metabolism, Ligands, Lymphocyte Activation, Lymphocyte Function-Associated Antigen-1/metabolism, T-Lymphocytes/cytology, Th2 Cells/cytology, Tumor Necrosis Factor-alpha/metabolism",
author = "Bleijs, {D A} and {de Waal-Malefyt}, R and Figdor, {C G} and {van Kooyk}, Y",
year = "1999",
month = "7",
doi = "10.1002/(SICI)1521-4141(199907)29:07<2248::AID-IMMU2248>3.0.CO;2-9",
language = "English",
volume = "29",
pages = "2248--58",
journal = "European Journal of Immunology",
issn = "0014-2980",
publisher = "Wiley-VCH Verlag",
number = "7",

}

Co-stimulation of T cells results in distinct IL-10 and TNF-alpha cytokine profiles dependent on binding to ICAM-1, ICAM-2 or ICAM-3. / Bleijs, D A; de Waal-Malefyt, R; Figdor, C G; van Kooyk, Y.

In: European Journal of Immunology, Vol. 29, No. 7, 07.1999, p. 2248-58.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Co-stimulation of T cells results in distinct IL-10 and TNF-alpha cytokine profiles dependent on binding to ICAM-1, ICAM-2 or ICAM-3

AU - Bleijs, D A

AU - de Waal-Malefyt, R

AU - Figdor, C G

AU - van Kooyk, Y

PY - 1999/7

Y1 - 1999/7

N2 - The LFA-1 adhesion molecule is involved in cell adhesion events of leukocytes through binding to ICAM-1, ICAM-2 and ICAM-3. Whether binding to either of these ligands similarly affects co-stimulation of T cells and cytokine secretion is unknown. We demonstrated that LFA-1 co-stimulation under suboptimal concentrations of anti-CD3 monoclonal antibodies resulted in high, intermediate and weak proliferation of T cells on ICAM-1, -2, and -3, respectively, which correlates with the distinct affinities of LFA-1 for these ligands. Furthermore, we investigated whether binding to ICAM-1, -2 or -3 induced different cytokine profiles, thus regulating T helper cell function. Granulocyte-macrophage colony-stimulating factor and IFN-gamma were secreted in high amounts, whereas IL-2, IL-4 and IL-5 could not be detected. Interestingly, we observed that LFA-1/ICAM-1 co-stimulation of T cells resulted in high production of the Th2 cytokine IL-10 compared to ICAM-2 or ICAM-3 co-stimulation. In contrast, ICAM-2 and ICAM-3 induced a much stronger secretion of the Th1 cytokine TNF-alpha compared to LFA-1/ICAM-1 induced co-stimulation, despite the lower proliferation rate. These results demonstrate that besides facilitating cell adhesion, LFA-1 serves as a potent co-stimulatory molecule by inducing different cytokine patterns depending on the ligand bound.

AB - The LFA-1 adhesion molecule is involved in cell adhesion events of leukocytes through binding to ICAM-1, ICAM-2 and ICAM-3. Whether binding to either of these ligands similarly affects co-stimulation of T cells and cytokine secretion is unknown. We demonstrated that LFA-1 co-stimulation under suboptimal concentrations of anti-CD3 monoclonal antibodies resulted in high, intermediate and weak proliferation of T cells on ICAM-1, -2, and -3, respectively, which correlates with the distinct affinities of LFA-1 for these ligands. Furthermore, we investigated whether binding to ICAM-1, -2 or -3 induced different cytokine profiles, thus regulating T helper cell function. Granulocyte-macrophage colony-stimulating factor and IFN-gamma were secreted in high amounts, whereas IL-2, IL-4 and IL-5 could not be detected. Interestingly, we observed that LFA-1/ICAM-1 co-stimulation of T cells resulted in high production of the Th2 cytokine IL-10 compared to ICAM-2 or ICAM-3 co-stimulation. In contrast, ICAM-2 and ICAM-3 induced a much stronger secretion of the Th1 cytokine TNF-alpha compared to LFA-1/ICAM-1 induced co-stimulation, despite the lower proliferation rate. These results demonstrate that besides facilitating cell adhesion, LFA-1 serves as a potent co-stimulatory molecule by inducing different cytokine patterns depending on the ligand bound.

KW - Antigens, CD/metabolism

KW - Antigens, Differentiation

KW - Cell Adhesion

KW - Cell Adhesion Molecules/metabolism

KW - Humans

KW - In Vitro Techniques

KW - Intercellular Adhesion Molecule-1/metabolism

KW - Interleukin-10/metabolism

KW - Ligands

KW - Lymphocyte Activation

KW - Lymphocyte Function-Associated Antigen-1/metabolism

KW - T-Lymphocytes/cytology

KW - Th2 Cells/cytology

KW - Tumor Necrosis Factor-alpha/metabolism

U2 - 10.1002/(SICI)1521-4141(199907)29:07<2248::AID-IMMU2248>3.0.CO;2-9

DO - 10.1002/(SICI)1521-4141(199907)29:07<2248::AID-IMMU2248>3.0.CO;2-9

M3 - Article

VL - 29

SP - 2248

EP - 2258

JO - European Journal of Immunology

JF - European Journal of Immunology

SN - 0014-2980

IS - 7

ER -