Effect of phorbol ester and calcium ionophore on human thymocytes

Positive selection of immature thymocytes is a developmental process in which TCR ligation with low avidity induces generation of mature T cells. In mouse thymocytes, CD4 +8 + double-positive (DP) cells which were treated with a proper combination of calcium ionophore ionomycin and phorbol 12-myrist...

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Bibliographic Details
Published in:Human immunology 2001-08, Vol.62 (8), p.771-781
Main Authors: Tanahashi, Masayuki, Yokoyama, Tomoki, Kobayashi, Yoshihiro, Yamakawa, Yosuke, Maeda, Masanobu, Fujii, Yoshitaka
Format: Article
Language:English
Subjects:
Antigens, CD1 - immunology
Apoptosis - drug effects
bcl-2
calcium ionophores
CD1 antigen
CD4 antigen
CD4 Antigens - analysis
CD4 down-regulation
CD8 Antigens - analysis
Cell Division - drug effects
Cell Survival
Cells, Cultured
Dexamethasone - pharmacology
Dose-Response Relationship, Immunologic
Flow Cytometry
Humans
ionomycin
Ionomycin - pharmacology
Ionophores - pharmacology
Lymphocyte Activation - drug effects
phorbol 12-myristate 13-acetate
Phorbol Esters - pharmacology
positive selection
protein kinase C
Proto-Oncogene Proteins c-bcl-2 - analysis
Proto-Oncogene Proteins c-bcl-2 - biosynthesis
T-Lymphocytes - drug effects
T-Lymphocytes - immunology
Thymus Gland - drug effects
Thymus Gland - immunology
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Summary:Positive selection of immature thymocytes is a developmental process in which TCR ligation with low avidity induces generation of mature T cells. In mouse thymocytes, CD4 +8 + double-positive (DP) cells which were treated with a proper combination of calcium ionophore ionomycin and phorbol 12-myristate 13-acetate (PMA) have been reported to differentiate into CD4 single positive cells. However, in human thymocytes the effects of PMA and ionomycin have remained unclear. Here we report that DP cells that were treated with PMA and ionomycin up-regulated bcl-2 and down-regulated CD1 expression. However, CD3 expression remained low. This treatment induced prolonged CD4 down-regulation in DP cells which was an effect also seen in mature peripheral blood T cells. PMA/ionomycin-treated DP cells showed high cell proliferation and resistance to dexamethasone-induced apoptosis. These results indicate that PKC activation and calcium elevation may be part of the biochemical signals that induce positive selection of human DP cells and the system described in this paper may be a useful model to study the signals involved in the selection of human thymocytes.
ISSN:0198-8859
1879-1166
DOI:10.1016/S0198-8859(01)00276-2