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Title: CD4 expression decrease by antisense oligonucleotides. Inhibition of rat T CD4+ cell reactivity
Author: Rabanal i Tornero, Manel
Franch i Masferrer, Àngels
Noé Mata, Verónica
Pelegrí i Gabaldà, Carme
Ciudad i Gómez, Carlos Julián
Castellote i Bargalló, M. Cristina
Castell, Margarida
Keywords: Cicle cel·lular
Cèl·lules sanguínies
Rates (Animals de laboratori)
Cell cycle
Blood cells
Rats as laboratory animals
Issue Date: Aug-2003
Publisher: Mary Ann Liebert, Inc.
Abstract: In previous studies, we have demonstrated the inhibition of CD4 expression in rat lymphocytes treated with phorbol myristate acetate (PMA) by antisense oligonucleotides (AS-ODNs) directed against the AUG start region of the cd4 gene. The aim of the present study was to inhibit CD4 expression in lymphocytes without promoting CD4 synthesis and to determine the effect of this inhibition on CD4+ T cell function. Four 21-mer ODNs against the rat cd4 gene (AS-CD4-1 to AS-CD4-4) were used. Surface CD4 expression was measured by immunofluorescence staining and flow cytometry, and mRNA CD4 expression was measured by RT-PCR. T CD4+ cell function was determined by specific and unspecific proliferative response of rat-primed lymphocytes. After 24 hours of incubation, AS-CD4-2 and AS-CD4-4 reduced lymphocyte surface CD4 expression by 40%. This effect remained for 72 hours and was not observed on other surface molecules, such as CD3, CD5, or CD8. CD4 mRNA expression was reduced up to 40% at 24 hours with AS-CD4-2 and AS-CD4-4. After 48 hours treatment, CD4 mRNA decreased up to 27% and 29% for AS-CD4-2 and AS-CD4-4, respectively. AS-CD4-2 and AS-CD4-4 inhibited T CD4+ cell proliferative response upon antigen-specific and unspecific stimuli. Therefore, AS-ODNs against CD4 molecules inhibited surface and mRNA CD4 expression, under physiologic turnover and, consequently, modulate T CD4+ cell reactivity.
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It is part of: Oligonucleotides, 2003, vol. 13, num. 4, p. 217-228
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ISSN: 1545-4576
Appears in Collections:Articles publicats en revistes (Bioquímica i Biomedicina Molecular)
Articles publicats en revistes (Bioquímica i Fisiologia)

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