Inhibition of cytotoxic T cell development by transforming growth factor beta and reversal by recombinant tumor necrosis factor alpha.

The Journal of experimental medicine ·Vol. 166 ·No. 4 ·1987-10-01 ·Pages 991-8

Ranges GE, Figari IS, Espevik T, Palladino MA

Abstract

The immunoregulatory effects of transforming growth factor beta (TGF-beta) and recombinant murine tumor necrosis factor alpha (rMuTNF-alpha) on CTL generation and activity were examined. The results demonstrate that TGF-beta, in a dose-dependent manner, inhibited CTL generation but not CTL activity. The inhibitory effects were detected only when TGF-beta was added within the first 48 h of the MLC. Little activity was seen when it was added thereafter, including the addition of TGF-beta to the cytotoxicity assay. The production of TNF-alpha, which occurs during early phases of the MLC and which is inhibited in the presence of TGF-beta, appears to have an important regulatory role, as altering the levels of TNF-alpha in an MLC can significantly influence CTL development. The inhibitory effects of TGF-beta on the MLC can be significantly reversed by the addition of rMuTNF-alpha to the cultures. These results demonstrate that TGF-beta can inhibit MLC and subsequent CTL generation at early stages of the reaction, and such inhibition may involve the suppression of TNF-alpha production.

MeSH Terms

Animals Antibodies Female Kinetics Mice Mice, Inbred BALB C Mice, Inbred C57BL Peptides/pharmacology Recombinant Proteins/pharmacology T-Lymphocytes, Cytotoxic/cytology,drug effects Transforming Growth Factors Tumor Necrosis Factor-alpha/pharmacology

Chemicals

Antibodies Peptides Recombinant Proteins Tumor Necrosis Factor-alpha Transforming Growth Factors

Authors & Affiliations

4 authors, click to expand affiliations / ORCID

Ranges G E

Department of Molecular Immunology, Genentech, Inc., South San Francisco, California 94080.

Figari I S

Espevik T

Palladino M A

References (19)

19 references, click to expand

Ontogeny of murine T lymphocytes. I. Maturation of thymocytes induced in vitro by tumor necrosis factor-positive serum (TNF+)1,2.
Cell Immunol. 1981 Jan 1;57(1):237-50 PMID: 6971158
Inhibition of cytokine production by cyclosporin A and transforming growth factor beta.
J Exp Med. 1987 Aug 1;166(2):571-6 PMID: 3110354
Lymphokine-mediated induction of cytolytic activity in a T cell hybridoma.
J Immunol. 1985 Jan;134(1):397-403 PMID: 3917280
Cloning and expression of cDNA for human lymphotoxin, a lymphokine with tumour necrosis activity.
Nature. 1984 Dec 20-1985 Jan 2;312(5996):721-4 PMID: 6334807
Human tumour necrosis factor: precursor structure, expression and homology to lymphotoxin.
Nature. 1984 Dec 20-1985 Jan 2;312(5996):724-9 PMID: 6392892
Lymphokine-induced cytotoxicity: requirement of two lymphokines for the induction of optimal cytotoxic response.
J Immunol. 1985 Jun;134(6):3912-9 PMID: 3921614
Effect of interleukin 2, interferon-gamma, and mitogens on the production of tumor necrosis factors alpha and beta.
J Immunol. 1985 Oct;135(4):2492-7 PMID: 3928750
Cloning and expression in Escherichia coli of the cDNA for murine tumor necrosis factor.
Proc Natl Acad Sci U S A. 1985 Sep;82(18):6060-4 PMID: 3898078
Recombinant human tumor necrosis factor-alpha: effects on proliferation of normal and transformed cells in vitro.
Science. 1985 Nov 22;230(4728):943-5 PMID: 3933111
Synergy between recombinant interleukin 2 (rIL 2) and IL 2-depleted lymphokine-containing supernatants in facilitating allogeneic human cytolytic T lymphocyte responses in vitro.
J Immunol. 1986 Feb 15;136(4):1274-82 PMID: 2418110
Production of transforming growth factor beta by human T lymphocytes and its potential role in the regulation of T cell growth.
J Exp Med. 1986 May 1;163(5):1037-50 PMID: 2871125
Transforming growth factor-beta: biological function and chemical structure.
Science. 1986 Aug 1;233(4763):532-4 PMID: 3487831
BSC-1 growth inhibitor/type beta transforming growth factor is a strong inhibitor of thymocyte proliferation.
Proc Natl Acad Sci U S A. 1986 Aug;83(15):5531-3 PMID: 3488549
Natural killer-sensitive targets stimulate production of TNF-alpha but not TNF-beta (lymphotoxin) by highly purified human peripheral blood large granular lymphocytes.
J Immunol. 1986 Oct 15;137(8):2592-8 PMID: 3760569
Transforming growth factor beta is an important immunomodulatory protein for human B lymphocytes.
J Immunol. 1986 Dec 15;137(12):3855-60 PMID: 2878044
A highly sensitive cell line, WEHI 164 clone 13, for measuring cytotoxic factor/tumor necrosis factor from human monocytes.
J Immunol Methods. 1986 Dec 4;95(1):99-105 PMID: 3782828
Immunoregulatory activity of recombinant human tumor necrosis factor (TNF)-alpha: induction of TNF receptors on human T cells and TNF-alpha-mediated enhancement of T cell responses.
J Immunol. 1987 Mar 15;138(6):1786-90 PMID: 3029221
Sequence of the porcine transforming growth factor-beta precursor.
Nucleic Acids Res. 1987 Apr 10;15(7):3187 PMID: 3470708
Induction of cytotoxic T cell function requires sequential action of three different lymphokines.
J Immunol. 1983 Jun;130(6):2508-10 PMID: 6602167

Article Info

Journal

The Journal of experimental medicine

Abbr.

J Exp Med

ISSN

0022-1007

DOI

10.1084/jem.166.4.991

Published

1987-10-01

Pages

991-8

Language

English

Region

United States

NLM ID

2985109R

PMCID

PMC2188710

Subset

External Links

PubMed source DOI: 10.1084/jem.166.4.991 PMC Full Text View journal details

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Inhibition of cytotoxic T cell development by transforming growth factor beta and reversal by recombinant tumor necrosis factor alpha.

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