DOI: 10.1084/jem.185.12.2053. A New Mechanism of NK Cell Cytotoxicity Activation: The CD40

A New Mechanism of NK Cell Cytotoxicity Activation: The CD40–CD40 Ligand Interaction

10.1084/jem.185.12.2053

Crossref journal-article

Rockefeller University Press

The Journal of Experimental Medicine (291)

Abstract

NK recognition is regulated by a delicate balance between positive signals initiating their effector functions, and inhibitory signals preventing them from proceeding to cytolysis. Knowledge of the molecules responsible for positive signaling in NK cells is currently limited. We demonstrate that IL-2–activated human NK cells can express CD40 ligand (CD40L) and that recognition of CD40 on target cells can provide an activation pathway for such human NK cells. CD40-transfected P815 cells were killed by NK cell lines expressing CD40L, clones and PBLderived NK cells cultured for 18 h in the presence of IL-2, but not by CD40L-negative fresh NK cells. Cross-linking of CD40L on IL-2–activated NK cells induced redirected cytolysis of CD40-negative but Fc receptor-expressing P815 cells. The sensitivity of human TAP-deficient T2 cells could be blocked by anti-CD40 antibodies as well as by reconstitution of TAP/MHC class I expression, indicating that the CD40-dependent pathway for NK activation can be downregulated, at least in part, by MHC class I molecules on the target cells. NK cell recognition of CD40 may be important in immunoregulation as well as in immune responses against B cell malignancies.

Bibliography

Carbone, E., Ruggiero, G., Terrazzano, G., Palomba, C., Manzo, C., Fontana, S., Spits, H., KÃ¤rre, K., & Zappacosta, S. (1997). A New Mechanism of NK Cell Cytotoxicity Activation: The CD40âCD40 Ligand Interaction. The Journal of Experimental Medicine, 185(12), 2053â2060.

Authors 9

Ennio Carbone (first)
Giuseppina Ruggiero (additional)
Giuseppe Terrazzano (additional)
Carmen Palomba (additional)
Ciro Manzo (additional)
Silvia Fontana (additional)
Hergen Spits (additional)
Klas Kärre (additional)
Serafino Zappacosta (additional)

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 12:49 p.m.)
Deposited	2 years, 1 month ago (July 25, 2023, 3:39 a.m.)
Indexed	1 month, 3 weeks ago (July 3, 2025, 5:06 a.m.)
Issued	28 years, 2 months ago (June 16, 1997)
Published	28 years, 2 months ago (June 16, 1997)
Published Online	28 years, 2 months ago (June 16, 1997)
Published Print	28 years, 2 months ago (June 16, 1997)

Funders 0

None

BibTeX

@article{Carbone_1997, title={A New Mechanism of NK Cell Cytotoxicity Activation: The CD40–CD40 Ligand Interaction}, volume={185}, ISSN={1540-9538}, url={http://dx.doi.org/10.1084/jem.185.12.2053}, DOI={10.1084/jem.185.12.2053}, number={12}, journal={The Journal of Experimental Medicine}, publisher={Rockefeller University Press}, author={Carbone, Ennio and Ruggiero, Giuseppina and Terrazzano, Giuseppe and Palomba, Carmen and Manzo, Ciro and Fontana, Silvia and Spits, Hergen and Kärre, Klas and Zappacosta, Serafino}, year={1997}, month=jun, pages={2053–2060} }

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