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A role of calcineurin in coreceptor regulation during differentiation of Cd4+Cd8+ T cells.

Abstract：

:The immunosuppressant FK506 inhibits thymocyte positive selection. Calcineurin, a FK506-sensitive Ca2+/calmodulin-dependent protein phosphatase, is presumed to be involved in this event without direct evidence. We have previously shown that moderate stimulation of CD4(+)CD8(+) thymocytes with a combination of the calcium ionophore ionomycin and phorbol myristate acetate mimics positive selection events including downregulation of CD8 expression. Moderate stimulation of a CD4(+)CD8(+) T cell line with the same combination of drugs also induced specific downregulation of CD8 expression. FK506 inhibited the CD8 downregulation in both cell types. The T cell line was transfected with an expression vector encoding an active form of calcineurin. The transfectans remained CD4(+)CD8(+), but became CD4(+)CD8(-) or CD4(+)CD8(low) upon stimulation with phorbol myristate acetate alone. The extent of the CD8 downregulation was correlated with the expression level of the mutant calcineurin. These results suggest that the calcium signal for the CD8 downregulation is mainly delivered through calcineurin activation.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Kuwata T,Asada A,Ohoka Y,Mukai M,Miyaike M,Iwata M

doi

10.1006/bbrc.1998.8767

subject

Has Abstract

pub_date

1998-06-18 00:00:00

pages

242-8

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(98)98767-8

journal_volume

247

pub_type

杂志文章

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