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. 2002:3:1.
doi: 10.1186/1471-2172-3-1. Epub 2002 Jan 18.

Phorbol esters and cAMP differentially regulate the expression of CD4 and CD8 in human thymocytes

Hector Martinez-Valdez  1 , Vicente Madrid-Marina, Amos Cohen
Affiliations

Phorbol esters and cAMP differentially regulate the expression of CD4 and CD8 in human thymocytes

Hector Martinez-Valdez et al. BMC Immunol. 2002.

Abstract

Background: Intrathymic development and selection of the T lymphocyte repertoire is restricted by the interactions of the T cell antigen receptor and CD4 or CD8 co-receptors with self major histocompatibility complex molecules. Positive or negative selection depends on a tight regulatory control of CD4 and CD8 expression. Determining the intracellular signals that differentially regulate the expression of CD4 and CD8 is important to understand the mechanisms that are implicated in selection of single positive CD4+CD8- or CD4-CD8+.

Results: The present study shows that stimulation of human thymocytes by phorbol esters or cAMP result in a differential regulation of CD4 and CD8 expression, both at the mRNA and cell surface glycoprotein level.

Conclusions: The differential regulation of CD4 and CD8 gene expression suggests that the selective activation of protein kinase C (PKC) and cAMP-dependent protein kinases (PKA) may be required for the selection of single positive CD4+CD8- and CD4-CD8+ cells during Intrathymic differentiation.

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Figures

Figure 1
Figure 1
Northern blot analysis of the effect of PMA and cAMP on CD4 and CD8 mRNA levels in human thymocytes. Cells were incubated for 4 h at 37°C in culture media as described in the methods, in the absence (lane 1) or in the presence of 10 nM PMA (lane 2) or 1 mM dibutyryl cAMP plus 1 mM IBMX (lane 3), and the combination of both (lane 4). RNA was subsequently extracted and analyzed. The expression of the proto-oncogene c-Ha-ras served as an internal control.
Figure 2
Figure 2
Northern blot to determine the specificity of the Phorbol ester effect on the expression of CD3, CD4, CD8, and C-Ha-ras by human thymocytes. Experimental conditions are number-coded as follows: 1 = control; 2 = PMA-treated; PDB-treated; 4 = α-Phorbol Ester-treated; and 5 = β-Phorbol Ester-treated.
Figure 3
Figure 3
Northern blot to examine the effect of cyclic AMP analogs and cholera toxin on CD4, CD8, and CD3 mRNA levels in human thymocytes. Experimental conditions are number-coded and respectively identified
Figure 4
Figure 4
Effect of PMA and cAMP on the surface expression of CD3, CD4, and CD8 by human thymocytes. (a) Immunofluorescent staining and (b) CD4 surface expression kinetics. Experimental conditions and detailed time course is respectively indicated.
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