Visilizumab induces apoptosis of mucosal T lymphocytes in ulcerative colitis through activation of caspase 3 and 8 dependent pathways

Qi T. Yu, Masayuki Saruta, Konstantinos Papadakis

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Visilizumab, a humanized low-Fc receptor binding anti-CD3 antibody, induces rapid clinical response in patients with steroid-refractory ulcerative colitis (UC). Several effective treatments in IBD have been linked to the induction of mucosal T cell apoptosis. The aim of the present study was to evaluate the effect of visilizumab on the apoptosis of lamina propria (LP) and peripheral blood (PB) lymphocytes isolated from patients with UC. Visilizumab induced dose- and time-dependent apoptosis of LP T cells isolated from non-IBD individuals, UC or CD patients. Maximal effect was seen at a concentration of 100 ng/ml and it was 33% for normal, 34% for UC and 23% for CD LP T cells following 24 h stimulation. Visilizumab induced apoptosis predominantly of CD4+ LP T cells, whereas CD8+ LP T cells were relatively resistant to apoptosis. Visilizumab did not induce apoptosis of PB T cells from UC patients. Visilizumab-induced apoptosis of LP T cells was dependent on caspase 3 and 8, but not caspase 9 activation and did not involve the Fas/FasL pathway. Low-Fc receptor binding Abs such as visilizumab may be highly effective for the treatment of UC through induction of apoptosis of LP T cells and rapid elimination of lesional pathogenic T cells in the gut mucosa.

Original languageEnglish (US)
Pages (from-to)322-329
Number of pages8
JournalClinical Immunology
Volume127
Issue number3
DOIs
StatePublished - Jun 1 2008
Externally publishedYes

Fingerprint

Caspase 8
Ulcerative Colitis
Caspase 3
Mucous Membrane
Apoptosis
T-Lymphocytes
Fc Receptors
visilizumab
Caspase 9
Anti-Idiotypic Antibodies
Blood Cells
Steroids
Lymphocytes
Therapeutics

Keywords

  • Apoptosis
  • Crohn's Disease
  • Inflammatory Bowel diseases
  • Low-Fc receptor binding anti-CD3 antibodies
  • Mucosal T Lymphocytes
  • Ulcerative colitis
  • Visilizumab

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Visilizumab induces apoptosis of mucosal T lymphocytes in ulcerative colitis through activation of caspase 3 and 8 dependent pathways. / Yu, Qi T.; Saruta, Masayuki; Papadakis, Konstantinos.

In: Clinical Immunology, Vol. 127, No. 3, 01.06.2008, p. 322-329.

Research output: Contribution to journalArticle

@article{24c0802e88f644a5a9c3e2d027bd8201,
title = "Visilizumab induces apoptosis of mucosal T lymphocytes in ulcerative colitis through activation of caspase 3 and 8 dependent pathways",
abstract = "Visilizumab, a humanized low-Fc receptor binding anti-CD3 antibody, induces rapid clinical response in patients with steroid-refractory ulcerative colitis (UC). Several effective treatments in IBD have been linked to the induction of mucosal T cell apoptosis. The aim of the present study was to evaluate the effect of visilizumab on the apoptosis of lamina propria (LP) and peripheral blood (PB) lymphocytes isolated from patients with UC. Visilizumab induced dose- and time-dependent apoptosis of LP T cells isolated from non-IBD individuals, UC or CD patients. Maximal effect was seen at a concentration of 100 ng/ml and it was 33{\%} for normal, 34{\%} for UC and 23{\%} for CD LP T cells following 24 h stimulation. Visilizumab induced apoptosis predominantly of CD4+ LP T cells, whereas CD8+ LP T cells were relatively resistant to apoptosis. Visilizumab did not induce apoptosis of PB T cells from UC patients. Visilizumab-induced apoptosis of LP T cells was dependent on caspase 3 and 8, but not caspase 9 activation and did not involve the Fas/FasL pathway. Low-Fc receptor binding Abs such as visilizumab may be highly effective for the treatment of UC through induction of apoptosis of LP T cells and rapid elimination of lesional pathogenic T cells in the gut mucosa.",
keywords = "Apoptosis, Crohn's Disease, Inflammatory Bowel diseases, Low-Fc receptor binding anti-CD3 antibodies, Mucosal T Lymphocytes, Ulcerative colitis, Visilizumab",
author = "Yu, {Qi T.} and Masayuki Saruta and Konstantinos Papadakis",
year = "2008",
month = "6",
day = "1",
doi = "10.1016/j.clim.2008.02.009",
language = "English (US)",
volume = "127",
pages = "322--329",
journal = "Clinical Immunology",
issn = "1521-6616",
publisher = "Academic Press Inc.",
number = "3",

}

TY - JOUR

T1 - Visilizumab induces apoptosis of mucosal T lymphocytes in ulcerative colitis through activation of caspase 3 and 8 dependent pathways

AU - Yu, Qi T.

AU - Saruta, Masayuki

AU - Papadakis, Konstantinos

PY - 2008/6/1

Y1 - 2008/6/1

N2 - Visilizumab, a humanized low-Fc receptor binding anti-CD3 antibody, induces rapid clinical response in patients with steroid-refractory ulcerative colitis (UC). Several effective treatments in IBD have been linked to the induction of mucosal T cell apoptosis. The aim of the present study was to evaluate the effect of visilizumab on the apoptosis of lamina propria (LP) and peripheral blood (PB) lymphocytes isolated from patients with UC. Visilizumab induced dose- and time-dependent apoptosis of LP T cells isolated from non-IBD individuals, UC or CD patients. Maximal effect was seen at a concentration of 100 ng/ml and it was 33% for normal, 34% for UC and 23% for CD LP T cells following 24 h stimulation. Visilizumab induced apoptosis predominantly of CD4+ LP T cells, whereas CD8+ LP T cells were relatively resistant to apoptosis. Visilizumab did not induce apoptosis of PB T cells from UC patients. Visilizumab-induced apoptosis of LP T cells was dependent on caspase 3 and 8, but not caspase 9 activation and did not involve the Fas/FasL pathway. Low-Fc receptor binding Abs such as visilizumab may be highly effective for the treatment of UC through induction of apoptosis of LP T cells and rapid elimination of lesional pathogenic T cells in the gut mucosa.

AB - Visilizumab, a humanized low-Fc receptor binding anti-CD3 antibody, induces rapid clinical response in patients with steroid-refractory ulcerative colitis (UC). Several effective treatments in IBD have been linked to the induction of mucosal T cell apoptosis. The aim of the present study was to evaluate the effect of visilizumab on the apoptosis of lamina propria (LP) and peripheral blood (PB) lymphocytes isolated from patients with UC. Visilizumab induced dose- and time-dependent apoptosis of LP T cells isolated from non-IBD individuals, UC or CD patients. Maximal effect was seen at a concentration of 100 ng/ml and it was 33% for normal, 34% for UC and 23% for CD LP T cells following 24 h stimulation. Visilizumab induced apoptosis predominantly of CD4+ LP T cells, whereas CD8+ LP T cells were relatively resistant to apoptosis. Visilizumab did not induce apoptosis of PB T cells from UC patients. Visilizumab-induced apoptosis of LP T cells was dependent on caspase 3 and 8, but not caspase 9 activation and did not involve the Fas/FasL pathway. Low-Fc receptor binding Abs such as visilizumab may be highly effective for the treatment of UC through induction of apoptosis of LP T cells and rapid elimination of lesional pathogenic T cells in the gut mucosa.

KW - Apoptosis

KW - Crohn's Disease

KW - Inflammatory Bowel diseases

KW - Low-Fc receptor binding anti-CD3 antibodies

KW - Mucosal T Lymphocytes

KW - Ulcerative colitis

KW - Visilizumab

UR - http://www.scopus.com/inward/record.url?scp=45249104849&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=45249104849&partnerID=8YFLogxK

U2 - 10.1016/j.clim.2008.02.009

DO - 10.1016/j.clim.2008.02.009

M3 - Article

C2 - 18424236

AN - SCOPUS:45249104849

VL - 127

SP - 322

EP - 329

JO - Clinical Immunology

JF - Clinical Immunology

SN - 1521-6616

IS - 3

ER -