In vivo inhibition of NF-kappa B in T-lineage cells leads to a dramatic decrease in cell proliferation and cytokine production and to increased cell apoptosis in response to mitogenic stimuli, but not to abnormal thymopoiesis

V Ferreira; N Sidénius; N Tarantino; P Hubert; L Chatenoud; F Blasi; M Körner

In vivo inhibition of NF-kappa B in T-lineage cells leads to a dramatic decrease in cell proliferation and cytokine production and to increased cell apoptosis in response to mitogenic stimuli, but not to abnormal thymopoiesis

J Immunol. 1999 Jun 1;162(11):6442-50.

Authors

V Ferreira¹, N Sidénius, N Tarantino, P Hubert, L Chatenoud, F Blasi, M Körner

Affiliation

¹ Laboratoire d'Immunologie Cellulaire et Tissulaire, Centre National de la Recherche Scientifique UMR 7627, Hôpital de la Pitié-Salpêtrière, Paris, France.

PMID: 10352258

Abstract

To understand the role of NF-kappa B complexes in T cell development and activation, we have generated transgenic mice in which RelA and c-Rel complexes were selectively inhibited in the T-lineage cells by specific expression of a trans-dominant form of I kappa B alpha. Transgene expression did not affect the thymic development, but led to lowered numbers of splenic T cells and to a dramatic decrease in the ex vivo proliferative response of splenic T lymphocytes. Analysis of IL-2 and IL-2R alpha expression demonstrated that the perturbation of the proliferation response was not attributable to an abnormal expression of these genes. In contrast, expression of IL-4, IL-10, and IFN-gamma was strongly inhibited in the transgenic T cells. The proliferative deficiency of the transgenic T cells was associated with an increased apoptosis. These results point out the involvement of NF-kappa B/Rel family proteins in growth signaling pathways by either regulating proteins involved in the IL-2 signaling or by functionally interfering with the cell cycle progression.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis / genetics
Apoptosis / immunology*
Cell Differentiation / genetics
Cell Differentiation / immunology
Cell Division / genetics
Cell Division / immunology
Cytokines / antagonists & inhibitors*
Cytokines / biosynthesis
DNA-Binding Proteins / biosynthesis
DNA-Binding Proteins / genetics
DNA-Binding Proteins / physiology*
Female
Humans
I-kappa B Proteins*
Interferon-gamma / biosynthesis
Interleukin-10 / biosynthesis
Interleukin-2 / biosynthesis
Interleukin-4 / biosynthesis
Ionomycin / pharmacology
Lymphocyte Activation / drug effects
Lymphocyte Activation / genetics
Male
Mice
Mice, Inbred C57BL
Mice, Inbred CBA
Mice, Transgenic
Mitogens / pharmacology*
NF-KappaB Inhibitor alpha
NF-kappa B / antagonists & inhibitors*
Receptors, Interleukin-2 / biosynthesis
T-Lymphocytes / cytology
T-Lymphocytes / immunology
T-Lymphocytes / metabolism*
Tetradecanoylphorbol Acetate / pharmacology
Thymus Gland / cytology
Thymus Gland / immunology
Thymus Gland / physiology*
Transgenes / immunology

Substances

Cytokines
DNA-Binding Proteins
I-kappa B Proteins
Interleukin-2
Mitogens
NF-kappa B
NFKBIA protein, human
Nfkbia protein, mouse
Receptors, Interleukin-2
Interleukin-10
NF-KappaB Inhibitor alpha
Interleukin-4
Ionomycin
Interferon-gamma
Tetradecanoylphorbol Acetate