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

Biochemical and Biophysical Research Communications
T KuwataM Iwata

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.

References

Jul 1, 1979·Proceedings of the National Academy of Sciences of the United States of America·E NakayamaL J Old
Jan 1, 1989·Advances in Immunology·B J Fowlkes, D M Pardoll
Feb 1, 1996·The Journal of Experimental Medicine·B W ZhangJ G Seidman
Oct 1, 1996·European Journal of Immunology·C C O'SheaM J Owen
Dec 9, 1997·Immunity·L L SharpS M Hedrick
Mar 24, 1998·Trends in Pharmacological Sciences·S H SnyderP D Suzdak

❮ Previous
Next ❯

Citations

May 9, 2000·The Journal of Biological Chemistry·S AdachiM Iwata

❮ Previous
Next ❯

Related Concepts

Related Feeds

Calcium & Bioenergetics

Bioenergetic processes, including cellular respiration and photosynthesis, concern the transformation of energy by cells. Here is the latest research on the role of calcium in bioenergetics.