In 1972, Jerry T. Thornthwaite presented a poster session with Professor, Dr. Bob Leif, at the annual Reticuloendothelial Society Meeting. The poster presented very unusual cells from the spleen (and later from the lymph nodes) of non-immunized mice that destroyed sheep red blood cells (SRBC) on contact. Thornthwaite came close to publishing the article in Science, but the conclusion proved it was more suitable for immunology journals and was later accepted.

Defining the name of these cells was a challenge, but he was able to develop a way of enumerating them, determining density and enrichment in the linear bovine serum albumiin gradidents and study the morphology using light and scanning electrons. Years later, Dr. Thornthwaite developed a clinical application by in vitro enriching natural killer cells for infusion into patients.

He investigated natural substances that were supposed to increase the natural killer cell response.

Unlike complement mediated IgM antibody destruction of SRBC, which showed lyses of "plaques" of SRBC appearing as deflated balloons (Fig. 1), the complete destruction of the SRBC did not require prior immunization with SRBC or complement (Fig. 2). Thus, Thornthwaite gave them the name "complement independent plaque-forming cells" (CIPFC) or "rough lymphocyte plaque-forming cells" when he was able to perform scanning electron microscopy (SEM). Later, Heberman (1973) and Oldham (1973) used the term "Natural Killer Cell".

In 1973, Thornthwaite developed a technique using alcian blue to stain cells that were dead prior to glutaraldehyde fixation. Viable cells, prior to glutaraldehyde fixation, did not stain. This technique was used to locate the Natural Killer Cell destroying target tumor cells. The killed tumor cells were also easy to see at the later stages by the blebbing of the membranes of the tumor cells (Fig. 3 and 4).

Working with Marilyn Cayer, they were able to section en face the alcian blue areas and perform electron microscopy.

Natural Killer Lymphocytes

Natural killer (NK) cells are antigen nonspecific lymphocytes which recognize foreign cells of many different antigenic types. These cells are an important first line of defense against newly malignant cells and cells infected with viruses, bacteria, and protozoa (Natural Killer Cells). About 5 to 16 percent of the total lymphocyte population contains natural killer cells. NK cells have the ability to attack foreign cells without first having to recognize specific antigens. It has been proposed that NK cells complement cytotoxic T-cells by taking charge in situations where MHC class I expression is hindered through the effects of virus infection (Nature, 1995).

NK cells have evolved a mechanism for mediating host defense against infection with viruses by having the ability to distinguish infected from uninfected cells. Although the exact mechanism is not clear at the present time, one possible mechanism may be that NK cells selectively kill target cells bearing low levels of MHC class I molecules on their surface. Natural killer cells have two types of surface receptor which aid in distinguishing infected from uninfected cells.

An NK cell kills a target cell by releasing perforin (and other molecules) which damages the target cell membrane leading to death. NK cells also cause death by inducing apoptosis," the process of" programmed cell death, in the target.

Natural killer (NK) cells are well known for their ability to kill certain tumors. However, it is now appreciated that NK cells have a significant role in host defense against invading pathogens, particularly intracellular organisms, and are capable of influencing the specific, acquired immune response. The ultimate goal of our work is to elucidate the function of NK cells in normal and abnormal immune responses and to derive targeted therapeutic interventions that influence these innate effector cells.