ORIGINAL ARTICLE: Ligation of CD8 alpha on human natural killer cells prevents activation-induced apoptosis and enhances cytolytic activity

• Published in: Immunology Vol. 116; no. 3; pp. 354 - 361
• Main Authors: Addison, Elena G, North, Janet, Bakhsh, Ismail, Marden, Chloe, Haq, Sumaira, Al-Sarraj, Samia, Malayeri, Reza, Wickremasinghe, RGitendra, Davies, Jeffrey K, Lowdell, Mark W
• Format: Journal Article
• Language: English
• Published: 01-11-2005
• ISSN: 0019-2805; 1365-2567
• DOI: 10.1111/j.1365-2567.2005.02235.x

It has been previously shown that the subset of human natural killer (NK) cells which express CD8 in a homodimeric alpha - alpha form are more cytotoxic than their CD8 super(-) counterparts but the mechanisms behind this differential cytolytic activity remained unknown. Target cell lysis by CD8 super(-) NK cells is associated with high levels of effector cell apoptosis, which is in contrast to the significantly lower levels found in the CD8 alpha super(+) cells after lysis of the same targets. We report that cross-linking of the CD8 alpha chains on NK cells induces rapid rises in intracellular Ca super(2+) and increased expression of CD69 at the cell surface by initiating the influx of extracellular Ca super(2+) ions. We demonstrate that secretion of cytolytic enzymes initiates NK-cell apoptosis from which CD8 alpha super(+) NK cells are protected by an influx of exogenous calcium following ligation of CD8 on the NK-cell surface. This ligation is through interaction with fellow NK cells in the cell conjugate and can occur when the target cells lack major histocompatibility complex (MHC) Class I expression. Protection from apoptosis is blocked by preincubation of the NK cells with anti-MHC Class I antibody. Thus, in contrast to the CD8 super(-) subset, CD8 alpha super(+) NK cells are capable of sequential lysis of multiple target cells.