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Ligation of CD8α on human natural killer cells prevents activation‐induced apoptosis and enhances cytolytic activity
Author(s) -
Addison Elena G.,
North Janet,
Bakhsh Ismail,
Marden Chloe,
Haq Sumaira,
AlSarraj Samia,
Malayeri Reza,
Wickremasinghe R. Gitendra,
Davies Jeffrey K.,
Lowdell Mark W.
Publication year - 2005
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2005.02235.x
Subject(s) - cytotoxic t cell , cytolysis , microbiology and biotechnology , interleukin 21 , cd8 , biology , natural killer cell , lymphokine activated killer cell , mhc class i , janus kinase 3 , major histocompatibility complex , interleukin 12 , nk 92 , natural killer t cell , immunology , antigen , biochemistry , in vitro
Summary It has been previously shown that the subset of human natural killer (NK) cells which express CD8 in a homodimeric α/α form are more cytotoxic than their CD8 – counterparts but the mechanisms behind this differential cytolytic activity remained unknown. Target cell lysis by CD8 – NK cells is associated with high levels of effector cell apoptosis, which is in contrast to the significantly lower levels found in the CD8α + cells after lysis of the same targets. We report that cross‐linking of the CD8α chains on NK cells induces rapid rises in intracellular Ca 2+ and increased expression of CD69 at the cell surface by initiating the influx of extracellular Ca 2+ ions. We demonstrate that secretion of cytolytic enzymes initiates NK‐cell apoptosis from which CD8α + 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 – subset, CD8α + NK cells are capable of sequential lysis of multiple target cells.