In vitro activated CD4+ T cells from interferon-gamma (IFN-gamma)-deficient mice induce intestinal inflammation in immunodeficient hosts.

S Bregenholt; J Brimnes; Mogens Holst Nissen; M H Claesson

In vitro activated CD4+ T cells from interferon-gamma (IFN-gamma)-deficient mice induce intestinal inflammation in immunodeficient hosts.

S Bregenholt, J Brimnes, Mogens Holst Nissen, M H Claesson

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

23 Citationer (Scopus)

Abstract

Udgivelsesdato: 1999-Nov

Originalsprog	Engelsk
Tidsskrift	Clinical and Experimental Immunology
Vol/bind	118
Udgave nummer	2
Sider (fra-til)	228-34
Antal sider	6
ISSN	0009-9104
Status	Udgivet - 1999

Bibliografisk note

Keywords: Animals; Apoptosis; CD4-Positive T-Lymphocytes; Cell Division; Cells, Cultured; Cytokines; Histocompatibility Antigens Class II; Immunity, Mucosal; Immunocompromised Host; Inflammatory Bowel Diseases; Interferon Type II; Intestinal Mucosa; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Mice, Knockout; Mice, SCID

Citationsformater

@article{b3bc5150ba3111ddae57000ea68e967b,

title = "In vitro activated CD4+ T cells from interferon-gamma (IFN-gamma)-deficient mice induce intestinal inflammation in immunodeficient hosts.",

abstract = "To investigate the role of IFN-gamma in the immunopathogenesis of inflammatory bowel disease (IBD), severe combined immunodeficient (SCID) mice were transplanted with in vitro activated CD4+ T cells from either wild-type (WT) or IFN-gamma-deficient (IFN-gammaKO) BALB/c mice. In vitro, the two types of T cells displayed comparable proliferation rates and production of tumour necrosis factor-alpha (TNF-alpha), IL-2, IL-4 and IL-10 after concanavalin A (Con A) stimulation. When transplanted into SCID mice, WT CD4+ blasts induced a lethal IBD, whereas IFN-gammaKO blasts induced a less severe intestinal inflammation with moderate weight loss. Intracellular cytokine staining of lamina propria lymphocytes (LPL) revealed comparable fractions of CD4+ T cells positive for TNF-alpha, IL-2 and IL-10 in the two groups of transplanted SCID mice, whereas a two-to-three-fold increase in the fraction of IL-4-positive cells was found in IFN-gammaKO-transplanted SCID mice. Flow cytometric analyses showed strong up-regulation of MHC class II expression of colonic epithelial cells of WT-CD4+ T cell-transplanted compared with IFN-gammaKO-transplanted SCID mice. A significantly higher fraction of CD4+ LPL were found to enter the cell cycle, i.e. to incorporate bromo-deoxy-uridine, and to undergo apoptosis in vivo in WT-transplanted compared with IFN-gammaKO-transplanted SCID mice. These data point towards an important role for IFN-gamma in the development of IBD in SCID mice. The inflammation might be initiated and subsequently enhanced by the ability of IFN-gamma to induce de novo MHC class II expression in the colonic epithelium, a change which could lead to increased antigen processing and production of local proinflammatory cytokines, CD4+ T cell turnover and thereby to exaggeration of disease.",

author = "S Bregenholt and J Brimnes and Nissen, {Mogens Holst} and Claesson, {M H}",

note = "Keywords: Animals; Apoptosis; CD4-Positive T-Lymphocytes; Cell Division; Cells, Cultured; Cytokines; Histocompatibility Antigens Class II; Immunity, Mucosal; Immunocompromised Host; Inflammatory Bowel Diseases; Interferon Type II; Intestinal Mucosa; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Mice, Knockout; Mice, SCID",

year = "1999",

language = "English",

volume = "118",

pages = "228--34",

journal = "Clinical and Experimental Immunology",

issn = "0009-9104",

publisher = "Wiley-Blackwell",

number = "2",

}

TY - JOUR

T1 - In vitro activated CD4+ T cells from interferon-gamma (IFN-gamma)-deficient mice induce intestinal inflammation in immunodeficient hosts.

AU - Bregenholt, S

AU - Brimnes, J

AU - Nissen, Mogens Holst

AU - Claesson, M H

N1 - Keywords: Animals; Apoptosis; CD4-Positive T-Lymphocytes; Cell Division; Cells, Cultured; Cytokines; Histocompatibility Antigens Class II; Immunity, Mucosal; Immunocompromised Host; Inflammatory Bowel Diseases; Interferon Type II; Intestinal Mucosa; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Mice, Knockout; Mice, SCID

PY - 1999

Y1 - 1999

N2 - To investigate the role of IFN-gamma in the immunopathogenesis of inflammatory bowel disease (IBD), severe combined immunodeficient (SCID) mice were transplanted with in vitro activated CD4+ T cells from either wild-type (WT) or IFN-gamma-deficient (IFN-gammaKO) BALB/c mice. In vitro, the two types of T cells displayed comparable proliferation rates and production of tumour necrosis factor-alpha (TNF-alpha), IL-2, IL-4 and IL-10 after concanavalin A (Con A) stimulation. When transplanted into SCID mice, WT CD4+ blasts induced a lethal IBD, whereas IFN-gammaKO blasts induced a less severe intestinal inflammation with moderate weight loss. Intracellular cytokine staining of lamina propria lymphocytes (LPL) revealed comparable fractions of CD4+ T cells positive for TNF-alpha, IL-2 and IL-10 in the two groups of transplanted SCID mice, whereas a two-to-three-fold increase in the fraction of IL-4-positive cells was found in IFN-gammaKO-transplanted SCID mice. Flow cytometric analyses showed strong up-regulation of MHC class II expression of colonic epithelial cells of WT-CD4+ T cell-transplanted compared with IFN-gammaKO-transplanted SCID mice. A significantly higher fraction of CD4+ LPL were found to enter the cell cycle, i.e. to incorporate bromo-deoxy-uridine, and to undergo apoptosis in vivo in WT-transplanted compared with IFN-gammaKO-transplanted SCID mice. These data point towards an important role for IFN-gamma in the development of IBD in SCID mice. The inflammation might be initiated and subsequently enhanced by the ability of IFN-gamma to induce de novo MHC class II expression in the colonic epithelium, a change which could lead to increased antigen processing and production of local proinflammatory cytokines, CD4+ T cell turnover and thereby to exaggeration of disease.

AB - To investigate the role of IFN-gamma in the immunopathogenesis of inflammatory bowel disease (IBD), severe combined immunodeficient (SCID) mice were transplanted with in vitro activated CD4+ T cells from either wild-type (WT) or IFN-gamma-deficient (IFN-gammaKO) BALB/c mice. In vitro, the two types of T cells displayed comparable proliferation rates and production of tumour necrosis factor-alpha (TNF-alpha), IL-2, IL-4 and IL-10 after concanavalin A (Con A) stimulation. When transplanted into SCID mice, WT CD4+ blasts induced a lethal IBD, whereas IFN-gammaKO blasts induced a less severe intestinal inflammation with moderate weight loss. Intracellular cytokine staining of lamina propria lymphocytes (LPL) revealed comparable fractions of CD4+ T cells positive for TNF-alpha, IL-2 and IL-10 in the two groups of transplanted SCID mice, whereas a two-to-three-fold increase in the fraction of IL-4-positive cells was found in IFN-gammaKO-transplanted SCID mice. Flow cytometric analyses showed strong up-regulation of MHC class II expression of colonic epithelial cells of WT-CD4+ T cell-transplanted compared with IFN-gammaKO-transplanted SCID mice. A significantly higher fraction of CD4+ LPL were found to enter the cell cycle, i.e. to incorporate bromo-deoxy-uridine, and to undergo apoptosis in vivo in WT-transplanted compared with IFN-gammaKO-transplanted SCID mice. These data point towards an important role for IFN-gamma in the development of IBD in SCID mice. The inflammation might be initiated and subsequently enhanced by the ability of IFN-gamma to induce de novo MHC class II expression in the colonic epithelium, a change which could lead to increased antigen processing and production of local proinflammatory cytokines, CD4+ T cell turnover and thereby to exaggeration of disease.

M3 - Journal article

C2 - 10540183

SN - 0009-9104

VL - 118

SP - 228

EP - 234

JO - Clinical and Experimental Immunology

JF - Clinical and Experimental Immunology

IS - 2

ER -