CD69 is a stimulatory receptor for natural killer cell and its cytotoxic effect is blocked by CD94 inhibitory receptor
Open Access
- 1 May 1999
- journal article
- research article
- Published by Wiley in Immunology
- Vol. 97 (1), 159-165
- https://doi.org/10.1046/j.1365-2567.1999.00738.x
Abstract
CD69 is a differentiation antigen expressed shortly after activation on T lymphocytes and other cells of haematopoietic origin, including natural killer (NK) cells. The function of CD69 on T lymphocytes acting as a costimulatory molecule in proliferation and lymphokine secretion is well established. NK cells express CD69 after activation by different stimuli such as phorbol 12-myristate 13-acetate (PMA), interleukin (IL)-2, IL-12, interferon-α (IFN-α) or anti-CD16 monoclonal antibodies (mAbs). However, although it has been shown that CD69 triggers NK-cell-mediated cytolytic activity, its effect on other NK-cell functions has not been studied. Furthermore, the possible interaction of CD69 triggering with other C-lectin type inhibitory receptors is not known. Thus, the objective of this work is to determine whether CD69-mediated NK cytotoxicity can be regulated by CD94 inhibitory receptor and the role of CD69 on other NK-cell functions different of cytotoxicity. The results show that CD69-mediated NK cytotoxicity can be abrogated by CD94 stimulation in NK cells expressing the CD94 inhibitory form of the receptor, indicating that CD94 regulates the cytotoxic events initiated by a wide variety of NK activatory receptors. We also show that anti-CD69 mAbs, not only triggered NK cytotoxicity, but also induce NK-cell proliferation, CD25 and intracellular adhesion molecule-1 (ICAM-1) expression, TNF-α production and Ca2+ mobilization in preactivated NK cells. These results suggest that CD69 plays a crucial role in NK-cell function contributing to sustain NK-cell activation, as it has been previously demonstrated in T cells.Keywords
This publication has 37 references indexed in Scilit:
- Structure and function of the CD94 C‐type lectin receptor complex involved in recognition of HLA class I moleculesImmunological Reviews, 1997
- Arousal and inhibition of human NK cellsImmunological Reviews, 1997
- Threonine 80 on HLA-B27 confers protection against lysis by a group of natural killer clonesEuropean Journal of Immunology, 1996
- The CD69 receptor: a multipurpose cell-surface trigger for hematopoietic cellsImmunology Today, 1994
- Differential Effects of IL12 and IL2 on Expression and Function of Cellular Adhesion Molecules on Purified Human Natural Killer CellsCellular Immunology, 1993
- Differential Effects of Tyrosine Kinase Inhibition in CD69 Antigen Expression and Lytic Activity Induced by rIL-2, rIL-12, and rIFN-α in Human NK CellsCellular Immunology, 1993
- Molecular characterization of the early activation antigen CD69: A type II membrane glycoprotein related to a family of natural killer cell activation antigensEuropean Journal of Immunology, 1993
- Tumor necrosis factor‐α production induced in T lymphocytes through the AIM/CD69 activation pathwayEuropean Journal of Immunology, 1992
- Response of human natural killer (NK) cells to NK cell stimulatory factor (NKSF): cytolytic activity and proliferation of NK cells are differentially regulated by NKSF.The Journal of Experimental Medicine, 1992
- Structure‐function relationship and immunochemical mapping of external and intracellular antigenic sites on the lymphocyte activation inducer molecule, AIM/CD69European Journal of Immunology, 1991