NK-like cells

NCC and NK-like cells have been reported to be involved in non-specific cell-mediated cytotoxicity (CMC) in fish. NCCs were originally described in channel catfish and are the most extensively studied killer cell population in teleosts. NCCs spontaneously kill a wide variety of target cells including tumour cells, virally transformed cells and protozoan parasites, and express components of the granule exocytosis pathway of CMC similar to mammalian cytotoxic lymphocytes (Froystad et al., 1998 Praveen et al., 2004). Catfish NCCs are small agranular lymphocytes that express a novel type III membrane protein termed the NCC receptor protein 1 (NCCRP-1) (Evans et al., 1984). NCC activity has been described in other fish species including rainbow trout, carp, damselfish and tilapia (Shen et al., 2002). 

LW, MILLER NW (2004), Identification and characterization of clonal NK-like cells from channel catfish (Ictalurus punctatus), Dev Comp Immunol, 28,139-52. 

Extranodal NK/T-cell lymphoma, nasal type Enteropathy-type T-cell lymphoma Hepatosplenic gamma-delta T-cell lymphoma Subcutaneous panniculitis-like T-cell lymphoma Mycosis fungoides/sezary syndrome... 

The p35 subunit of IL-12 is produced by T and B cells, NK cells, neutrophils, monocytes, and macrophages (at least in the mouse). The p40 subunit is produced mainly by B lymphocytes, activated monocytes, and dendritic cells (including epidermal Langerhans cells). Consequently the principal sources of IL-12 are B cells and monocytes and/or macrophages (Figure 22-20). In the brain, microglia-like cells are the primary producers of the p40 transcripts. In contrast, the IL-12 p35 gene is constitutively expressed in the brain at a very low level. ... 

This pair of granule-associated proteins is also localized to cytotoxic T and NK cells. They are essential for both apoptosis and induced cell death of target cells via induction of perforated cell membranes. However, their expression is assumed to be evidence of an activated state. They mark subcutaneous panniculitis-like T-cell lymphoma, aggressive NK-cell leukemia, and extra-nodal NK/T cell lymphoma, nasal type. 

Interferons induce a wide range of biological effects. Generally, type I interferons induce similar effects, which are distinct from the effects induced by IFN-y. The most pronounced effect of type I interferons relates to their antiviral activity, as well as their anti-proliferative effect on various cell types, including certain tumour cell types. Anti-tumour effects are likely due not only to a direct anti-proliferative effect on the tumour cells themselves, but also due to the ability of type I interferons to increase NK and T-cytotoxic cell activity. These cells can recognize and destroy cancer cells. 

Additional molecular mechanisms must also mediate IFN-y effects, as it promotes a marked clinical improvement in some CGD patients without enhancing phagocyte activity. IFN-y s demonstrated ability to stimulate aspects of cellular and humoral immunity (e.g. via T- and B-lymphocytes), as well as NK cell activity, is most likely responsible for these observed improvements. 

NK cells, which, like some T-cells, can induce lysis of tumour cells. The tumouricidal activity of NK cells is potentiated by various cytokines (e.g. IL-2 and TNF). 

The theoretical complications posed by random chromosomal integration became a medical reality in 2002, when two children who had received retroviral-based gene therapy 2 years previously developed a leukaemic-like condition. The initial clinical trial aimed to treat X-linked severe combined immunodeficiency (SCID-X1), a hereditary disorder in which T-lymphocytes and NK cells in particular do not develop, due to a mutation in the gene coding for the yc cytokine receptor subunit. The clinical consequence is near abolition of a functional immune system. 

The receptor for RANKL is RANK, also known as ODAR (Anderson et al. 1997 Hsu et al. 1999). RANK is expressed in osteoclast precursors, mature osteoclasts, condrocytes, fibroblasts, and immune system cells (Anderson et al. 1997 Hsu et al. 1999). The binding of RANKL with RANK on preosteoclasts initiates the OCS and the activation of osteoclasts (Anderson et al. 1997 Hsu et al. 1999 Nakagawa et al. 1998). RANK-deficient mice display a phenotype characterized by osteopetrosis and several defects in the immune system similar to that observed in RANKL-deficient mice (Dougall et al. 1999). Consistent with this hypothesis, RANK-deficient mice are resistant to bone resorption induced by TNF-a, IL-l/J, or vitamin D3 (Li et al. 2000). In agreement with this, mice deficient in molecules implied in the transduction pathway from RANK like TRAF-6 or NF-/c Bl/NK-/c B2 also show an osteopetrotic phenotype,... 

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