Biology Reference
In-Depth Information
ch 15
Natural killer cells in graft-
versus-host disease and
graft-versus-leukemia
Bree Foley
Department of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, Minnesota, USA
Maite Alvarez
Department of Dermatology, University of California at Davis School of Medicine, Sacramento, California, USA
William Murphy
Department of Dermatology, University of California at Davis School of Medicine, Sacramento, California, USA
Jeffrey S Miller
Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, Minnesota, USA
327
Introduction
Natural killer (NK) cells were first described in mice in 1964 as an activ-
ity by which lethally irradiated mice and mice without prior sensitization
could resist bone marrow (BM) allografts [1] . Furthermore, this rejection
ability did not follow the classical laws of transplantation in that paren-
tal BM allografts were resisted by F1 hybrid recipients in a phenomenon
termed “hybrid resistance” [2] ( Figure 15.1 ). The radioresistant host effec-
tor cells were capable of mediating resistance to BM but not solid tissue
allografts, suggesting that a new cell type existed. The demonstration of
human NK cell activity, first detected in vitro in 1975 with human periph-
eral blood mononuclear cells by non-major histocompatibility complex
(MHC)-restricted cytotoxicity toward transformed or virally infected target
cells, heralded the era of NK cell biology. The unique receptor system uti-
lized by these cells would later account for the “peculiar” immunogenet-
ics of BM allograft resistance. It was these early experiments that led Karre
and colleagues to formulate the “missing self hypothesis”, in which NK cell
cytotoxicity is triggered by the loss of MHC class I on the tumor cells [3] . Fol-
lowing this observation various families of receptors were identified on NK
cells that recognize MHC class I that mediate tolerance in the host. Because
of their ability to lyse tumors with aberrant MHC class I expression and pro-
duce cytokines and chemokines upon activation, NK cells have immense
therapeutic potential to treat cancer.
In humans, NK cells are identified by the expression of the cell adhe-
sion marker CD56 and lack of the T-cell receptor, CD3, and are found
in many tissues, including the spleen, BM lymph nodes, and peripheral
 
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