Natural cytotoxicity in the neonate: high levels of lymphokine activated killer (LAK) activity.

In 28 healthy full-term newborns the percentage of circulating cells expressing the Leu7 antigen, the marker of natural killer (NK) cells, was significantly lower than in healthy adults. However, newborns and adults did not differ with regard to the percentage of cells reacting with the Leulla, Leullc and TEC NK-1, monoclonal antibodies directed against the IgG Fc receptor of killer cells. Spontaneous NK activity of neonatal cells was profoundly reduced compared to the adult. In contrast, antibody dependent cellular cytotoxicity and NK-like activity generated in mixed lymphocyte cultures were similar in the two groups and lymphokine-activated killer cell (LAK) activity was high in the neonate. Natural killing is thought to play an important role in antiviral immunity since the neonate has a deficient capacity to deal with viral infections. Consequently, the present data indicate either that spontaneous NK is the most informative in vitro measure of newborn natural cytotoxicity in vivo, or, alternatively, that natural killing is not as important in antiviral immunity as previously suggeste

Natural cytotoxicity impairment in familial haemophagocytic lymphohistiocytosis.

Ten children with the characteristic clinical and haematological features of haemophagocytic lymphohistiocytosis are reported. Four patients treated with a combination of drugs comprising etoposide, methotrexate, and steroids were in complete remission after 10 to 30 months. Natural cytotoxic mechanisms including natural killer cell activity, antibody dependent cell mediated cytotoxicity, lymphokine activated killer cell activity, and natural killer cell like activity were persistently absent or severely impaired in these four patients despite their clinical remission. Their parents and one healthy sibling also had impaired natural cytotoxic mechanisms. Constitutional impairment of natural cytotoxic mechanisms could be important in the pathogenesis of haemophagocytic lymphohistiocytosis

Transplant of bone marrow and cord blood hematopoietic stem cells in children, revisited according to the fundamental principles of bioethics

The two most widely used sources of hematopoietic stem cells for allogeneic transplants in pediatric practice are bone marrow (BM) and cord blood (CB). While bone marrow transplantation (BMT) is reaching its 30th year of application, human umbilical cord blood transplantation (HUCBT) is approaching its 10th. Although these procedures have basically the same purpose, a number of biological differences distinguish them. In particular, the intrinsically limited quantity of CB stem cells and their immunological naiveté confer peculiar characteristics to these hematopoietic progenitors. From a bioethical point of view, the problems which have repeatedly been raised when the BM donor is a child are well-known. Different but no less important ethical problems are raised when one considers HUCBT; in this regard the most important issues are the easier propensity of programming a CB donor in comparison with a BM donor (clearly due to the shorter time interval needed to collect the hematopoietic progenitors); the in utero HLA-typing; the implication of employing 'blood belonging to a neonate' for a third party; the need to perform a number of investigations both on the CB of the donor and on the mother and the implications that the discovery of disease may have for them, but also the need to establish banks for storing CB, with the accompanying administration and management problems. All these different aspects of UCBT will be discussed in the light of the four fundamental and traditional principles of bioethics, namely autonomy, nonmaleficence, beneficence and justice

Ethical reappraisal of 15 years of cord blood transplantation

Since the first successful use of cord blood as source of haemopoietic stem cells for transplantation in 1988, more than 2000 patients with malignant or non-malignant disorders have been treated with this procedure. Collection and storage of cord blood has prompted ethical considerations, mainly dealing with the issues of autonomy in making decisions about donation of cord blood, and of privacy and confidentiality in the tests required before use of placental cells for transplantation. The ethical implications of possible storage of cord-blood cells for autologous use has also been discussed. Preimplantation selection of HLA-matched embryos to obtain a donor of cells for cord-blood transplantation of a sibling with a life-threatening disease has raised the issue of the extent to which this approach complies with the principles of bioethics