Home LiteratureArticle Details

PMID: 8676088 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

A critical role for transforming growth factor-beta but not interleukin 4 in the suppression of T helper type 1-mediated colitis by CD45RB(low) CD4+ T cells.

The Journal of experimental medicine ·Vol. 183 ·No. 6 ·1996-06-01 ·Pages 2669-74

Powrie F, Carlino J, Leach MW, Mauze S, Coffman RL

Abstract

A T helper type 1 (Th1)-mediated colitis with similarities to inflammatory bowel disease in humans developed in severe combined immunodeficiency mice reconstituted with CD45RB(high) CD4+ splenic T cells and could be prevented by cotransfer of CD45RB(low) CD4+ T cells. Inhibition of this Th1 response by the CD45RB(low) T cell population could be reversed in vivo by an anti-transforming growth factor (TGF) beta antibody. Interleukin (IL) 4 was not required for either the differentiation of function of protective cells as CD45RB(low) CD4+ cells from IL-4-deficient mice were fully effective. These results identify a subpopulation of peripheral CD4+ cells and TGF-beta as critical components of the natural immune regulatory mechanism, which prevents the development of pathogenic Th1 responses in the gut, and suggests that this immunoregulatory population is distinct from Th2 cells.

MeSH Terms

Animals Antibodies, Monoclonal/pharmacology CD4-Positive T-Lymphocytes/immunology Colitis/immunology,pathology,therapy Flow Cytometry Humans Interleukin-4/immunology,physiology Leukocyte Common Antigens Mice Mice, Inbred BALB C Mice, Mutant Strains Mice, SCID Protein Tyrosine Phosphatase, Non-Receptor Type 1 Spleen/immunology T-Lymphocytes/immunology Th1 Cells/immunology Transforming Growth Factor beta/immunology,physiology

Chemicals

Antibodies, Monoclonal Transforming Growth Factor beta Interleukin-4 Leukocyte Common Antigens Protein Tyrosine Phosphatase, Non-Receptor Type 1

Authors & Affiliations

5 authors, click to expand affiliations / ORCID

Powrie F

DNAX Research Institute of Molecular and Cellular Biology Inc., Palo Alto 94304, USA.

Carlino J

Leach M W

Mauze S

Coffman R L

References (28)

28 references, click to expand

Interleukin-10.
Annu Rev Immunol. 1993;11:165-90 PMID: 8386517
Evidence that the T cell repertoire of normal rats contains cells with the potential to cause diabetes. Characterization of the CD4+ T cell subset that inhibits this autoimmune potential.
J Exp Med. 1993 Mar 1;177(3):627-36 PMID: 8094734
CD4+ T cells that express high levels of CD45RB induce wasting disease when transferred into congenic severe combined immunodeficient mice. Disease development is prevented by cotransfer of purified CD4+ T cells.
J Exp Med. 1993 Jul 1;178(1):237-44 PMID: 8100269
Cytokine regulation of T-cell function: potential for therapeutic intervention.
Immunol Today. 1993 Jun;14(6):270-4 PMID: 8104408
Ulcerative colitis-like disease in mice with a disrupted interleukin-2 gene.
Cell. 1993 Oct 22;75(2):253-61 PMID: 8402910
Interleukin-10-deficient mice develop chronic enterocolitis.
Cell. 1993 Oct 22;75(2):263-74 PMID: 8402911
Spontaneous development of inflammatory bowel disease in T cell receptor mutant mice.
Cell. 1993 Oct 22;75(2):274-82 PMID: 8104709
Phenotypically distinct subsets of CD4+ T cells induce or protect from chronic intestinal inflammation in C. B-17 scid mice.
Int Immunol. 1993 Nov;5(11):1461-71 PMID: 7903159
Regulatory interactions between CD45RBhigh and CD45RBlow CD4+ T cells are important for the balance between protective and pathogenic cell-mediated immunity.
J Exp Med. 1994 Feb 1;179(2):589-600 PMID: 7905019
Acquisition of lymphokine-producing phenotype by CD4+ T cells.
Annu Rev Immunol. 1994;12:635-73 PMID: 7912089
Oral tolerance: immunologic mechanisms and treatment of animal and human organ-specific autoimmune diseases by oral administration of autoantigens.
Annu Rev Immunol. 1994;12:809-37 PMID: 8011298
Regulatory T cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis.
Science. 1994 Aug 26;265(5176):1237-40 PMID: 7520605
B7-1 and B7-2 costimulatory molecules activate differentially the Th1/Th2 developmental pathways: application to autoimmune disease therapy.
Cell. 1995 Mar 10;80(5):707-18 PMID: 7534215
Modulation of cytokine patterns of human autoreactive T cell clones by a single amino acid substitution of their peptide ligand.
Immunity. 1995 Apr;2(4):373-80 PMID: 7536622
Inhibition of Th1 responses prevents inflammatory bowel disease in scid mice reconstituted with CD45RBhi CD4+ T cells.
Immunity. 1994 Oct;1(7):553-62 PMID: 7600284
Prevention of experimental allergic encephalomyelitis in rats by targeting autoantigen to B cells: evidence that the protective mechanism depends on changes in the cytokine response and migratory properties of the autoantigen-specific T cells.
J Exp Med. 1995 Aug 1;182(2):335-44 PMID: 7543135
T cells in inflammatory bowel disease: protective and pathogenic roles.
Immunity. 1995 Aug;3(2):171-4 PMID: 7648390
Surface antigen expression and immunoglobulin gene rearrangement during mouse pre-B cell development.
Immunol Rev. 1982;69:5-23 PMID: 6984001
Organ-specific autoimmune diseases induced in mice by elimination of T cell subset. I. Evidence for the active participation of T cells in natural self-tolerance; deficit of a T cell subset as a possible cause of autoimmune disease.
J Exp Med. 1985 Jan 1;161(1):72-87 PMID: 3871469
Monoclonal antibodies recognizing transforming growth factor-beta. Bioactivity neutralization and transforming growth factor beta 2 affinity purification.
J Immunol. 1989 Mar 1;142(5):1536-41 PMID: 2537357
OX-22high CD4+ T cells induce wasting disease with multiple organ pathology: prevention by the OX-22low subset.
J Exp Med. 1990 Dec 1;172(6):1701-8 PMID: 2258700
Pathogenetic and clinical relevance of cytokines in inflammatory bowel disease.
Immunol Res. 1991;10(3-4):465-71 PMID: 1955773
Role of cytokines in the differentiation of CD4+ T-cell subsets in vivo.
Immunol Rev. 1991 Oct;123:189-207 PMID: 1684779
Suppressor T cells generated by oral tolerization to myelin basic protein suppress both in vitro and in vivo immune responses by the release of transforming growth factor beta after antigen-specific triggering.
Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):421-5 PMID: 1370356
Role of T-cell derived cytokines in the downregulation of immune responses in parasitic and retroviral infection.
Immunol Rev. 1992 Jun;127:183-204 PMID: 1354651
Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease.
Nature. 1992 Oct 22;359(6397):693-9 PMID: 1436033
Transforming growth factor beta 1 null mutation in mice causes excessive inflammatory response and early death.
Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):770-4 PMID: 8421714
Localization of transforming growth factor beta isoforms in the normal murine small intestine and colon.
Gastroenterology. 1993 Jul;105(1):67-73 PMID: 8514063

Article Info

Journal

The Journal of experimental medicine

Abbr.

J Exp Med

ISSN

0022-1007

DOI

10.1084/jem.183.6.2669

Published

1996-06-01

Pages

2669-74

Language

English

Region

United States

NLM ID

2985109R

PMCID

PMC2192626

Subset

External Links

PubMed source DOI: 10.1084/jem.183.6.2669 PMC Full Text View journal details

Analysis Services

A critical role for transforming growth factor-beta but not interleukin 4 in the suppression of T helper type 1-mediated colitis by CD45RB(low) CD4+ T cells.

Contact

WeChat Official Account