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We have analyzed the antibody repertoire from normo- and hypercholesterolemic subjects to investigate how it can be related to macrophage-dependent modification of low-density lipoproteins, in comparison to the commonly used copper-oxidized LDL. Preexisting natural antibodies in plasma from normo- and hypercholesterolemic individuals were tested for their reactivity against copper ion oxidized LDL and LDL modified by macrophages. A crosswise comparison between these two antigen preparations demonstrated a different antibody repertoire in normo- and hypercholesterolemic patients. This study suggest that the search for antibodies that can influence the progression or regression of an atherosclerotic process has to take into account the process by which LDL is modified, and the repertoire of antibodies that is generated in the normal population, in comparison to that with, or at risk for, coronary artery diseases.

We have used a bovine papilloma virus (BPV) based mammalian cell expression vector consisting of the complete BPV genome and a human cytomegalovirus transcription unit for the production of soluble CD4. Mouse C-127 cells were transfected with vector DNA together with a selectable G418 resistance plasmid. Surviving clones were selected for high production using a solid phase ELISA based on the immobilization of supernatant-derived CD4 onto nitrocellulose paper and subsequent detection with anti-CD4 antibodies. The expressed protein was shown to bind HIV-gp120 and efficiently block HIV-1 infection in vitro. The possibility to use the above system for rapid production of defined glycoprotein fragments harboring defined functional regions, for the further elucidation of the functional role of CD4 in antigen presentation and cell to cell contact, and for possible intervention during HIV infection is discussed.

NATURAL KILLER (NK) cells constitute a distinct subgroup of cells within the immune system1,2. They are found in the lymphoid organs of several species including man and are cytolytic on contact in short-term in vitro assays for several cell types, in particular tumour cells1–5. Although the level of NK cell activity is under genetic control6,7, several extraneous agents, including bacterial adjuvants, animal viruses and NK-sensitive tumour cells induce an increase in in vivo NK cell activity6–10. Several of these agents are also known to increase the resistance of mice to transplantable tumours. This effect may be mediated by NK cells, as a positive correlation exists between in vivo resistance to syngeneic tumours and the levels of NK cell activity in the individual mice11,12. Viruses as well as several immunoadjuvants are also inducers of interferon. Here we present evidence that interferon and interferon inducers markedly enhance NK cell activity in mice, and suggest that interferon may be the mediator by which many different agents increase NK cell activity in vivo.

Natural killer (NK) cells have unique surface features and physiological characteristics and a selective ability to lyse some, but not other, target cells1,2. However, the basis of this selectivity remains obscure at both effector and target cell levels. Proposed specific NK-cell target moieties3–5 include glycolipids, and glycoproteins unrelated to the major histocompatibility complex, while malignant and certain normal cells have been found to be susceptible to NK-cell-mediated cytolysis6–8. There is good evidence that NK cells can inhibit the outgrowth of small numbers of transplanted tumour cells in vivo9,10 and can restrict the establishment of secondary metastasis11,12. It has thus been speculated that NK cells function as a primitive, thymus-independent immune system using phylogenetically preserved target structures to form a cell-mediated resistance barrier against the outgrowth of certain tumour cells1. The presence in the thymuses of neonatal mice and humans8,13 and in the marrow of human fetuses, of apparently normal cells which are quite sensitive to NK cells suggested that NK cells might have an increased ability to cause the lysis of cells at a particular stage of their differentiation. In agreement with this concept, embryonal carcinoma cells at various stages of differentiation display a strikingly different susceptibility to NK-cell-induced lysis14. Here only cell types representing early stages were sensitive to NK-cell-mediated cytolysis, whereas the more differentiated endodermal cell lines showed close to complete resistance. The above data would thus support the view that, in vivo, depending on the stage of differentiation, both normal and malignant cells are under surveillance by NK cells. Here we have considered the question of differentiation-related NK-cell susceptibility using defined cell lines known to undergo controlled differentiation in the presence of various agents. Three tumour cell-lines were investigated, and all demonstrated a striking positive correlation between a decrease in NK-cell susceptibility and the induction of differentiation by the various inducers. Our findings support the view that susceptibility to NK-cell mediated lysis may vary according to the stage of differentiation of the target cell.

Mouse teratocarcinomas are tumours of the germ cells1 whose tumorigenicity is a property of a pluripotent stem cell type denoted the embryonal carcinoma (EC) cell. These cells seem to be analogous to cells of the early mouse embryo and will indeed contribute to the normal development of a mouse if injected into blastocysts2. EC cells display an unusual transplantation behaviour and can frequently be grafted, giving tumours in several different mouse strains3. Thus, the protective immune mechanisms against such tumours may be less efficient than, and/or of a different nature from, those against most other tissues. Cytolytic T cells generally fail to kill EC cells4–6, although there is one report of the apparent induction of specific anti-EC T-killer cells7. The failures4–6 are easily explained as being due to the absence of major histocompatibility complex (MHC) products on the surface of ECs3,8. Recently, however, a new cell type, the natural killer (NK) cell, has been shown to have potent lytic activity when tested against several tumour targets9–11. Targets of NK cells also include normal thymocytes12 and certain stem cells of the bone marrow13. As NK cells seem to display a select but distinct specificity pattern from T lymphocytes and because NK targets include normal cells at an ‘immature’ stage of differentiation, we considered it possible that NK cells provide an alternative to T cells in producing cell-mediated immune reactions against teratocarcinomas. Here we report that murine NK cells are highly efficient cytolytic aggressors to EC cells whereas more differentiated cell lines derived from the latter are less susceptible or completely resistant.