Initial Identification And Characterization Of Nk Cells

Natural killer (NK) cells are widely recognized as a major component of the immune system, which, in addition to specifically immune T cells, can play an important role in host defences against cancer and microbial infections. However, the recognition of the existence of NK cells and their extensive characterization has unfolded only during the past 30 years.

In the early 1970s, many tumour immunologists began to examine the ability of lymphocytes from tumour immune or tumour-bearing individuals to kill tumour cells in vitro. These studies were initially performed within the paradigm of expecting that specifically immune T cells, reactive against tumour associated antigens, would be detected. In parallel, studies were performed with lymphocytes of cancer patients, mainly in colony inhibition or microcytotoxicity assays, and with lymphocytes from tumour immunized mice or rats, mainly by the then recently developed assay of51 Cr release. In most of these studies, lymphocytes from normal individuals were included as controls, presumed to set the baseline against which the levels of cytotoxic reactivity of specifically immune T cells might be quantitatively assessed. However, in a variety of instances, the ability of lymphocytes of normal individuals was found to be as high as or even higher than that of lymphocytes from tumour-immunized or tumour-bearing individuals [1-10]. For example, the very first report of such observations may have been in a study of anti-leukaemia reactivity of human twins [1], in which not only the normal twin but also some normal adults were found to be able to kill leukaemic blast cells. Since such results were unexpected and did not fit the existing paradigm, the killing of tumour cells by lymphocytes from some normal individuals was mainly attributed to technical problems in the assays and a workshop was even held by the National Cancer Institute in 1972 [11] to discuss the issue. However, over the next 3—4 years, it became increasingly clear that the ability of some lymphocytes from normal individuals to kill tumour cells was a valid aspect of the tumour immunobiology of a variety of mammalian species, including humans [1-4], rats [5,6] and mice [7-10],

Once the existence of natural cell-mediated immunity began to be appreciated, considerable efforts were expended to determine the characteristics of the reactive lymphocytes [reviewed in 12], It was almost immediately clear that the normal lymphocytes responsible for the anti-tumour activity were not typical T cells, since nude, athymic mice had high levels of natural cell-medicated cytotoxic reactively. In fact, the initial characterization of the effector cells was one of exclusions, with the conclusion that they lacked the characteristic features of T cells, B cells, macrophages or polymorphonuclear neutrophils. Rather, the natural reactivity against tumours seemed attributable to a particular subpopulation of lymphoid cells that have been termed NK cells. The existence of NK cells rapidly attracted considerable attention by many immunologists and much of their early observations are summarized in two extensive books [13,14] and various reviews [e.g., 12,15],

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