The role of interleukin 2 and T11 E rosette antigen in activation and proliferation of human NK clones

Although considerable data have recently been accumulated regarding the functional role of natural killer (NK) cells, relatively little is known about the factors that regulate NK cell activity. In these studies, we evaluated the role of interleukin 2 (IL 2) and the expression of the IL 2 receptor in the activation and proliferation of human NK cloned cell lines. By using a series of cloned cell lines, we were able to analyze homogeneous populations of NK cells that ordinarily comprise only a small fraction of peripheral blood lymphocytes and are extremely heterogeneous with respect to phenotypes and cytotoxic specificities. In comparison with several T cell clones, we found a much lower density of IL 2 receptors on NK clones, regardless of whether or not these cloned cells had a mature T cell phenotype. Correspondingly, NK clones needed a 10-fold higher concentration of recombinant IL 2 for maximal proliferation. Moreover, blocking studies with specific monoclonal IL 2 receptor antibodies indicated that IL 2 is both necessary and sufficient to induce the proliferation of NK clones. Because the majority of peripheral blood NK cells and NK clones express the T11 E rosette receptor antigen, which has been shown to be an antigen-independent activation pathway for T cells, we were able to study the role of monoclonal anti-T11 antibodies in the activation of various NK clones for which a specific target antigen is not known. In contrast to T cell clones, the induction of IL 2 receptor expression after T11 activation was possible only for some NK clones such as JT10 and JT3, but not for CNK5. Before activation, the IL 2 receptor expression of NK clones was confined to cells in the G2 - M phase, but after T11 activation the more pronounced IL 2 receptor expression became independent of the cell cycle. With respect to the direct proliferative effect of anti-T11 activation that has been noted with T cell clones, only the T3+ (JT10) and not the T3- NK clones could be directly stimulated. Nevertheless, IL 2 receptor expression could be triggered on some T3- clones such as JT3. Because T11-induced proliferation of T cells has been shown to be dependent on both the expression of the IL 2 receptor and on the interaction of this receptor with IL 2, it is proposed that the different responses of NK cells to T11 activation may reflect the ability of the individual clone to produce endogenous IL 2, as well as its ability to express the IL 2 receptor.     

Health and the life course: why safety nets matter.

This article argues that a life course approach is necessary to understand social variations in health. This is needed in order to take into account the complex ways in which biological risk interacts with economic, social, and psychological factors in the development of chronic disease. Such an approach reveals biological and social "critical periods" during which social policies that will defend individuals against an accumulation of risk are particularly important. In many ways, the authors of modern welfare states were implicitly addressing these issues, and the contribution of these policies to present day high standards of health in developed countries should not be ignored.     

Endothelial cell junctions

In the course of a freeze-cleave study on intercellular junctions in the regenerating rat liver, we observed an unusual array of intramembranous particles located in regions of contact between endothelial cells lining the hepatic sinusoids. These arrays were characterized by an accumulation of particles which resembled a zonula occludens in their linear deployment but differed in that the contact regions were composed of individual particles which remained separated from each other by regular particle-free intervals.     

Roentgenographic and direct measurement of femoral cortical involution in a prehistoric Mississippian population

Recent roentgenographic studies suggest that periosteal apposition adds femoral cortical bone faster than it is lost by endosteal involution, so that cortical bone area increases with age. A comparison was made of direct and roentgenographic measurements of femoral cortical bone using femora from 23 females and 20 males of a prehistoric Mississippian population dated at A.D. 1540–1700. The comparison revealed that significant errors existed in the technique of radiographic measurement (p<0.000001), in estimating male and female cortical thickness (p<0.000001), and the changes in thickness with age (p<0.000001). There was no significant interaction of the variables: age, sex, and method. The errors arose partly from the inability of the roentgenograph to reveal clearly endosteal porosity, and partly in the assumption that the medial and lateral cortical wall thickness would be representative of the mean cortical thickness. The reduction in cortical thickness (11.3% males and 29.3% females) with age as measured directly is comparable with loss in modern populations.