Biology Reference
In-Depth Information
T A B L E
9.1. Properties and Functions of NK Cells
General Properties
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Lymphocytes from healthy individuals exhibit spontaneous cytotoxicity
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NK cells isolated from human peripheral blood kill certain targets (cancer, virally
infected)
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NK cells mediate ADCC through the CD16 receptor
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Antigen nonspeci®c
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No clonal speci®city
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No MHC restriction
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No immunological memory
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Dependent on intact bone marrow but not thymus
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No expression of T- or B-cell surface receptors
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Express inhibitory and activating receptors
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Light buoyant density (separate on Ficoll)
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De®ned as LGL (high plasma to nucleus ratio)ÐAzurophilic granules
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Constitute 3±15% of peripheral blood lymphocytes
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Do not appear to recirculate
.
NK activity augmented by various stimuli (microbial, IL-2, IL-12, IL-15,
interferon [IFN]-a, etc.)
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Augmented activity per cell basis; proliferation of percursors; redistribution
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NK interacts with endothelial cells (NK LFA-1ÐICAM-1)
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Mature NK cells are short lived, half life 1±2 days
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After bone marrow transplantation, NK are ®rst to reconstitute
NK Cell Functions
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Natural resistance against microbial and viral infections (important player in
non-adaptive immunity)
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Readily and rapidly responsive to biological response modi®ers
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Mediate killing of tumor cells in tissues by several distinct mechanisms
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Poised to produce a variety of cytokines
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Endowed with receptors that facilitate entry into solid tissues
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Exercises immunoregulatory control with respect to other immune cells
NK cells are present in the immature CD3
ÿ
CD4
ÿ
CD8
ÿ
thymocyte subset
isolated from the postnatal thymus. Further, polyclonal or clonal populations
can be isolated from human thymus that express phenotypic and functional
features that are intermediate between T and NK cells ( Poggi and Minagari,
1995).
Several reports have investigated the di¨erentiation of NK cells. The lack of
rearrangement of genes encoding antigen-speci®c receptors (Ig and TCR) dis-
tinguishes NK cells from B and T lymphocytes. Hence, mice de®cient in genes
encoding enzymes involved in recombination of antigen-speci®c receptors (e.g.,
RAG-2) lack both B and T lymphocytes but possess normal NK cells (Shinkai
et al., 1992). In contrast, mice de®cient in genes necessary for the development
of lymphoid cells (e.g., Ikaros) failed to develop mature NK cells and T and B
lymphocytes (Georgopoulos et al., 1994). These ®ndings suggest the presence of