Characteristics Of Nk Cells

A major advance in the characterization of NK cells came from the observation that both human and rat NK activity was attributable to lymphocytes with a distinct morphology, termed large granular lymphocytes (LGL) [16,17], LGL comprise about 5% of the peripheral blood or splenic leukocytes in man and other species and can be readily identified morphologically. They can be highly enriched by centrifugation on density gradients of Percoll [16,17]. The availability of such highly purified effector cell populations quickly led to the identification of distinct cell surface molecules on NK cells. Human NK cells can now be readily identified and quantitated among peripheral blood mononuclear cells, by flow cytometry, as CD3 CD56+ cells [18]. Similarly, rat NK cells are now mainly characterized by the presence of NKR.P1 [19] and mouse NK cells by the presence of NK1 [20], which is the mouse equivalent of NKR.P1.

The hallmark function of NK cells is their ability to spontaneously and rapidly kill a variety of tumour cells, especially leukaemia cells and certain tumour cell lines. Although most carcinomas and cell lines derived from solid tumours are resistant to51 Cr release cytotoxicity, which has been related to perforin-mediated damage, Vujanovic et al. [21] have recently found that such tumour cells undergo apoptotic cell death upon interaction with human NK cells. The NK cell is a quite selective killer, which does not harm normal "self" but can eliminate a wide range of NK-susceptible target cells, which include virus-infected normal cells as well as other tumour cells, without the need for antigen processing or presentation by major histocompatibility complex (MHC) molecules as is the case for cytotoxic T cells [22].

The basis for the selective target cell repertoire of NK cells is not completely understood.

It has been thought that NK cell-mediated killing is not MHC-restricted, but this concept has been challenged recently [23], Moretta and colleagues have provided evidence that NK cells show alloantigen specificity and that it is possible to define distinct alloantigen-reactive clones of NK cells [24], Thus, receptors specific for alloantigens encoded by the HLA-C or a closely linked gene are thought to be present on NK cells [24], The role of the MHC class I complex in the susceptibility of targets to NK-mediated lysis has been controversial. Transfection of MHC-deficient tumour cells with the MHC class I gene confers resistance to lysis by NK cells [25], and this resistance has been mapped to the a, and a2 domains of HLA-A2 molecules [26], It thus appears that expression of class I MHC molecules on target cells confers protection against NK cell lysis, while the absence of MHC molecules enhances susceptibility to lysis, as if NK cells were able to sense this absence ("missing-self hypothesis"). The possibility that a negative signal is delivered to NK cells by class 1 MHC molecules or MHC-associated ligands, inducing protection from NK-mediated lysis, provides an explanation of why NK cells are not harmful to self targets (i.e., normal tissue cells) and is consistent with the presence of alloantigen receptors on NK cells.

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