Granulocyte macrophage colony-stimulating factor treatment of a patient in myasthenic crisis: Effects on regulatory T cells

Abstract Macrophage colony stimulating factor (CSF-1) is one of several cytokines that control the differentiation, survival, and proliferation of monocytes and macrophages. A set of 11 human T-cell clones, chosen for their phenotypic diversity, were tested for their ability to express CSF-1 mRNA. After 5 hours of stimulation with phorbol myristate acetate (PMA) + calcium ionophore (Cal), all T-cell clones expressed a major 4-kb transcript, a less abundant 2-kb transcript, and several other minor species. This pattern of expression is typical for CSF-1 mRNAs. Furthermore, of the two alloreactive T-cell clones analyzed, only one showed a definitive message for CSF-1 on specific antigenic stimulation, but with delayed kinetics and less efficiency. Both conditions of stimulation induced the release of CSF-1 protein by T cells in the culture medium. Together, these findings demonstrate for the first time that normal T cells are able to produce CSF-1, previous reports being limited to two cases of tumoral cells of the T-cell lineage.

Download Full-text

NF-kappa B as inducible transcriptional activator of the granulocyte-macrophage colony-stimulating factor gene.

Molecular and Cellular Biology ◽

10.1128/mcb.10.3.1281 ◽

1990 ◽

Vol 10 (3) ◽

pp. 1281-1286 ◽

Cited By ~ 131

Author(s):

R Schreck ◽

P A Baeuerle

Keyword(s):

T Cells ◽

Transcription Factor ◽

T Cell ◽

Interleukin 2 ◽

Colony Stimulating Factor ◽

Nf Kappa B ◽

Gm Csf ◽

Macrophage Colony Stimulating Factor ◽

Macrophage Colony ◽

Stimulating Factor

The expression of the gene encoding the granulocyte-macrophage colony-stimulating factor (GM-CSF) is induced upon activation of T cells with phytohemagglutinin and active phorbolester and upon expression of tax1, a transactivating protein of the human T-cell leukemia virus type I. The same agents induce transcription from the interleukin-2 receptor alpha-chain and interleukin-2 genes, depending on promoter elements that bind the inducible transcription factor NF-kappa B (or an NF-kappa B-like factor). We therefore tested the possibility that the GM-CSF gene is also regulated by a cognate motif for the NF-kappa B transcription factor. A recent functional analysis by Miyatake et al. (S. Miyatake, M. Seiki, M. Yoshida, and K. Arai, Mol. Cell. Biol. 8:5581-5587, 1988) described a short promoter region in the GM-CSF gene that conferred strong inducibility by T-cell-activating signals and tax1, but no NF-kappa B-binding motifs were identified. Using electrophoretic mobility shift assays, we showed binding of purified human NF-kappa B and of the NF-kappa B activated in Jurkat T cells to an oligonucleotide comprising the GM-CSF promoter element responsible for mediating responsiveness to T-cell-activating signals and tax1. As shown by a methylation interference analysis and oligonucleotide competition experiments, purified NF-kappa B binds at positions -82 to -91 (GGGAACTACC) of the GM-CSF promoter sequence with an affinity similar to that with which it binds to the biologically functional kappa B motif in the beta interferon promoter (GGGAAATTCC). Two kappa B-like motifs at positions -98 to -108 of the GM-CSF promoter were also recognized but with much lower affinities. Our data provide strong evidence that the expression of the GM-CSF gene following T-cell activation is controlled by binding of the NF-kappa B transcription factor to a high-affinity binding site in the GM-CSF promoter.

Download Full-text

Expression of the macrophage-specific colony-stimulating factor in human monocytes treated with granulocyte-macrophage colony-stimulating factor

Blood ◽

10.1182/blood.v69.4.1259.bloodjournal6941259 ◽

1987 ◽

Vol 69 (4) ◽

pp. 1259-1261

Author(s):

J Horiguchi ◽

MK Warren ◽

D Kufe

Keyword(s):

T Cells ◽

Gene Product ◽

Phorbol Ester ◽

Human Monocytes ◽

Colony Stimulating Factor ◽

Gm Csf ◽

Macrophage Colony Stimulating Factor ◽

Activated Monocytes ◽

Macrophage Colony ◽

Stimulating Factor

The macrophage-specific colony-stimulating factor (CSF-1, M-CSF) regulates the survival, growth and differentiation of monocytes. We have recently demonstrated that phorbol ester induces expression of CSF- 1 in human monocytes. These findings suggested that activated monocytes are capable of producing their own lineage-specific CSF. The present studies demonstrate that the granulocyte-macrophage colony-stimulating factor (GM-CSF) also induces CSF-1 transcripts in monocytes. Furthermore, we demonstrate that the detection of CSF-1 RNA in GM-CSF- treated monocytes is associated with synthesis of the CSF-1 gene product. The results thus suggest that GM-CSF may indirectly control specific monocyte functions through the regulation of CSF-1 production. These findings indicate another level of interaction between T cells and monocytes.

Download Full-text

Differentiation of human dendritic cells from monocytes in vitro using granulocyte-macrophage colony stimulating factor and low concentration of interleukin-4

Vojnosanitetski pregled ◽

10.2298/vsp0305531c ◽

2003 ◽

Vol 60 (5) ◽

pp. 531-538 ◽

Cited By ~ 11

Author(s):

Miodrag Colic ◽

Dusan Jandric ◽

Zorica Stojic-Vukanic ◽

Jelena Antic-Stankovic ◽

Petar Popovic ◽

...

Keyword(s):

T Cells ◽

Interleukin 4 ◽

Adherent Cells ◽

Colony Stimulating Factor ◽

Gm Csf ◽

Alloreactive T Cells ◽

Macrophage Colony Stimulating Factor ◽

Macrophage Colony ◽

Human Dendritic Cells ◽

Stimulating Factor

Several laboratories have developed culture systems that allow the generation of large numbers of human dendritic cells (DC) from monocytes using granulocyte-macrophage colony stimulating factor (GM-CSF), and interleukin-4 (IL-4). In this work we provided evidence that GM-CSF (100 ng/ml) in combination with a low concentration of IL-4 (5 ng/ml) was efficient in the generation of immature, non-adherent, monocyte-derived DC as the same concentration of GM-CSF, and ten times higher concentration of IL-4 (50 ng/ml). This conclusion was based on the similar phenotype profile of DC such as the expression of CD1a, CD80, CD86, and HLA-DR, down-regulation of CD14, and the absence of CD83, as well as on their similar allostimulatory activity for T cells. A higher number of cells remained adherent in cultures with lower concentrations of IL-4 than in cultures with higher concentrations of the cytokine. However, most of these adherent cells down-regulated CD14 and stimulated the proliferation of alloreactive T cells. In contrast adherent cells cultivated with GM-CSF alone were predominantly macrophages as judged by the expression of CD14 and the inefficiency to stimulate alloreactive T cells. DC generated in the presence of lower concentrations of IL-4 had higher proapoptotic potential for the Jurkat cell line than DC differentiated with higher concentrations of IL-4, suggesting their stronger cytotoxic, anti-tumor effect.

Download Full-text