T cell suppression by osteoclasts in vitro

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

T cells are critical regulators of osteoclast differentiation and function in bone, but whether osteoclasts can, in turn, regulate T cell homing, and response to stimuli is unclear. To investigate whether osteoclasts are immune competent cells, the expression of HLA Class II and costimulatory receptors was evaluated by RT-PCR and immunohistochemistry by comparing osteoclast precursors and mature osteoclasts. T-cell-attracting chemokines were measured in the supernatants of confluent cultures of osteoclasts and compared with mesenchymal stromal cells and osteoblasts. T cell proliferation, cytokine production, and apoptosis were assayed in co-cultures with osteoclasts in the presence or absence of mitogenic stimuli. To define the mechanism of action of osteoclasts, cytokine-blocking experiments were performed. Our findings revealed that mature osteoclasts constitutively expressed Class II HLA in the membrane and upregulate the expression of CD40 and CD80 during differentiation. Osteoclasts secreted high levels of most T cell chemoattractants and effectively retained T cells in adhesion assays. Moreover, the osteoclasts potently blunted T cell response to PHA and CD3/CD28 stimulation, thus inhibiting proliferation, suppressing T cell TNFα and IFNγ production and decreasing T cell apoptosis by a mostly cell-contact independent mechanism. In conclusion, osteoclasts are immune-competent cells which can retain T cells and suppress in vitro T cell response to proliferative stimuli.

Original languageEnglish
Pages (from-to)982-990
Number of pages9
JournalJournal of Cellular Physiology
Volume226
Issue number4
DOIs
Publication statusPublished - Apr 2011

Fingerprint

T-cells
Osteoclasts
T-Lymphocytes
In Vitro Techniques
Apoptosis
Cytokines
Chemotactic Factors
Osteoblasts
Cell proliferation
Coculture Techniques
Mesenchymal Stromal Cells
Chemokines
Cell Adhesion
Assays
Bone
Up-Regulation
Adhesion
Immunohistochemistry
Cell Proliferation

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

T cell suppression by osteoclasts in vitro. / Grassi, Francesco; Manferdini, Cristina; Cattini, Luca; Piacentini, Anna; Gabusi, Elena; Facchini, Andrea; Lisignoli, Gina.

In: Journal of Cellular Physiology, Vol. 226, No. 4, 04.2011, p. 982-990.

Research output: Contribution to journalArticle

@article{3c86fa96feec402f9bf03a20c0bf1784,
title = "T cell suppression by osteoclasts in vitro",
abstract = "T cells are critical regulators of osteoclast differentiation and function in bone, but whether osteoclasts can, in turn, regulate T cell homing, and response to stimuli is unclear. To investigate whether osteoclasts are immune competent cells, the expression of HLA Class II and costimulatory receptors was evaluated by RT-PCR and immunohistochemistry by comparing osteoclast precursors and mature osteoclasts. T-cell-attracting chemokines were measured in the supernatants of confluent cultures of osteoclasts and compared with mesenchymal stromal cells and osteoblasts. T cell proliferation, cytokine production, and apoptosis were assayed in co-cultures with osteoclasts in the presence or absence of mitogenic stimuli. To define the mechanism of action of osteoclasts, cytokine-blocking experiments were performed. Our findings revealed that mature osteoclasts constitutively expressed Class II HLA in the membrane and upregulate the expression of CD40 and CD80 during differentiation. Osteoclasts secreted high levels of most T cell chemoattractants and effectively retained T cells in adhesion assays. Moreover, the osteoclasts potently blunted T cell response to PHA and CD3/CD28 stimulation, thus inhibiting proliferation, suppressing T cell TNFα and IFNγ production and decreasing T cell apoptosis by a mostly cell-contact independent mechanism. In conclusion, osteoclasts are immune-competent cells which can retain T cells and suppress in vitro T cell response to proliferative stimuli.",
author = "Francesco Grassi and Cristina Manferdini and Luca Cattini and Anna Piacentini and Elena Gabusi and Andrea Facchini and Gina Lisignoli",
year = "2011",
month = "4",
doi = "10.1002/jcp.22411",
language = "English",
volume = "226",
pages = "982--990",
journal = "Journal of cellular and comparative physiology",
issn = "0021-9541",
publisher = "Wiley-Liss Inc.",
number = "4",

}

TY - JOUR

T1 - T cell suppression by osteoclasts in vitro

AU - Grassi, Francesco

AU - Manferdini, Cristina

AU - Cattini, Luca

AU - Piacentini, Anna

AU - Gabusi, Elena

AU - Facchini, Andrea

AU - Lisignoli, Gina

PY - 2011/4

Y1 - 2011/4

N2 - T cells are critical regulators of osteoclast differentiation and function in bone, but whether osteoclasts can, in turn, regulate T cell homing, and response to stimuli is unclear. To investigate whether osteoclasts are immune competent cells, the expression of HLA Class II and costimulatory receptors was evaluated by RT-PCR and immunohistochemistry by comparing osteoclast precursors and mature osteoclasts. T-cell-attracting chemokines were measured in the supernatants of confluent cultures of osteoclasts and compared with mesenchymal stromal cells and osteoblasts. T cell proliferation, cytokine production, and apoptosis were assayed in co-cultures with osteoclasts in the presence or absence of mitogenic stimuli. To define the mechanism of action of osteoclasts, cytokine-blocking experiments were performed. Our findings revealed that mature osteoclasts constitutively expressed Class II HLA in the membrane and upregulate the expression of CD40 and CD80 during differentiation. Osteoclasts secreted high levels of most T cell chemoattractants and effectively retained T cells in adhesion assays. Moreover, the osteoclasts potently blunted T cell response to PHA and CD3/CD28 stimulation, thus inhibiting proliferation, suppressing T cell TNFα and IFNγ production and decreasing T cell apoptosis by a mostly cell-contact independent mechanism. In conclusion, osteoclasts are immune-competent cells which can retain T cells and suppress in vitro T cell response to proliferative stimuli.

AB - T cells are critical regulators of osteoclast differentiation and function in bone, but whether osteoclasts can, in turn, regulate T cell homing, and response to stimuli is unclear. To investigate whether osteoclasts are immune competent cells, the expression of HLA Class II and costimulatory receptors was evaluated by RT-PCR and immunohistochemistry by comparing osteoclast precursors and mature osteoclasts. T-cell-attracting chemokines were measured in the supernatants of confluent cultures of osteoclasts and compared with mesenchymal stromal cells and osteoblasts. T cell proliferation, cytokine production, and apoptosis were assayed in co-cultures with osteoclasts in the presence or absence of mitogenic stimuli. To define the mechanism of action of osteoclasts, cytokine-blocking experiments were performed. Our findings revealed that mature osteoclasts constitutively expressed Class II HLA in the membrane and upregulate the expression of CD40 and CD80 during differentiation. Osteoclasts secreted high levels of most T cell chemoattractants and effectively retained T cells in adhesion assays. Moreover, the osteoclasts potently blunted T cell response to PHA and CD3/CD28 stimulation, thus inhibiting proliferation, suppressing T cell TNFα and IFNγ production and decreasing T cell apoptosis by a mostly cell-contact independent mechanism. In conclusion, osteoclasts are immune-competent cells which can retain T cells and suppress in vitro T cell response to proliferative stimuli.

UR - http://www.scopus.com/inward/record.url?scp=79251501314&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79251501314&partnerID=8YFLogxK

U2 - 10.1002/jcp.22411

DO - 10.1002/jcp.22411

M3 - Article

VL - 226

SP - 982

EP - 990

JO - Journal of cellular and comparative physiology

JF - Journal of cellular and comparative physiology

SN - 0021-9541

IS - 4

ER -