Beta thalassemia: an immunologic therapy?
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Animals↗
Biomedical subjects
L S Rayfield
Publications and source records attributed to L S Rayfield.
Donor-reactive lymphocytes are opsonized in mice with passively enhanced skin allografts but not in tolerant mice.
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Animals↗
Suppression of natural cell-mediated cytotoxicity in man by maternal and neonatal serum.
the natural cytotoxicity of cells prepared from the blood of human neonates and women at the time of parturition was investigated, using a 4 hr 51Cr release assay and two established cell lines as targets. Although cord cells proved to be cytotoxic, the overall level was distinctly lower than that of normal adult cells. Whereas adult cells from males gave higher levels of cytotoxicity compared with cells from females, this was not the case for cord cells. Cells from women in labour showed even lower cytotoxic values. Neonatal and maternal serum or plasma caused a profound inhibition of the cytotoxicity shown by adult cells when present during the assay or following preincubation of effector cells with serum. Cord cells were not suppressed by either autologous or allogeneic cord sera. The nature of these suppressive factors and their origin and ontogeny remain to be elucidated. It would appear that in the neonate, and possibly also in the fetus, natural cytotoxicity is largely suppressed by serum factors, both in mother and offspring. This could represent yet another example of immunological modulation in pregnancy.
Adult↗
Supposed lamarckian inheritance of immunological tolerance.
The notion that an adaptation acquired during an organism's lifetime can somehow be imprinted on the genome and so become heritable has been faulted by every critical test to which it has hitherto been exposed, but many naturalists have lost their faith in what seems to them to be the all-encompassing explanatory glibness of neo-darwinism. Although this criticism is unfair it is entirely proper that neo-darwinism should be under constant critical scrutiny. Interest was therefore aroused by the claim of Gorczynski and Steele that tolerance of A strain antigens induced in CBA mice by injecting into them (CBA x A/J)F1 spleen and bone marrow cells could be transmitted down the male line. Such a claim is of particular interest because spermatozoa, unlike oocytes, are produced throughout life and might thus conceivably have participated in the mechanism envisaged by Steele as that responsible for the supposed transfer of genetic information from soma to germ plasm. It was claimed that as many as 60% of the progeny of tolerant fathers mated with normal CBA females were unresponsive or hyporesponsive in an in vitro assay in which their spleen cells were tested for reactivity against A/J strain histocompatibility antigens in the cell-mediated lympholysis assay (CML). We describe here our failure to confirm these findings and our inability to extend them by testing the progeny for their reactivity against skin allografts from the tolerance-conferring strain.
Adaptation, Physiological↗
Development of cell-mediated lympholysis in human foetal blood lymphocytes.
White cells from pure foetal blood obtained by fetoscopy, or from the cord at birth, were sensitized in mixed lymphocyte culture with irradiated adult peripheral blood lymphocytes. After 6-8 days of culture they were assayed in a standard 4-hr 51Cr-release cytotoxicity assay (CML) using lymphoblastoid cell targets from the stimulator cell donor. The age of the foetuses ranged from 15-22 weeks of gestation. Third-party target cells and adult blood served as controls. The mean cytotoxic responses of cord (11 donors) and adult (10 donors) blood lymphocytes were not significantly different and had similar kinetics. Foetal lymphocytes (25 donors) displayed a wide range of reactivity with half, scattered throughout the age range, totally negative and a further 23% with marginal responses. Definite cytotoxicity was found in the remainder, but not before the 18th week; these responses were evenly distributed in the range 18-22 weeks. Third-party responses were never more than one-quarter of the specific cytotoxicity. It was shown that the negative and very weak responses were almost certainly not due to technical factors. It is concluded that the majority of human foetuses in the range 15-22 weeks, though capable of giving clear mixed lymphocyte reactions, cannot develop full effector function as measured by the CML assay.
Adult↗
Abrogation of resistance to bone marrow transplantation by induction of specific tolerance in natural killer cells?
Hybrid resistance describes the capacity of first generation (F1) hybrids between certain mouse strains to inhibit the growth of tumour or haematopoietic cells of parental origin. The cells that appear to mediate this phenomenon differ from classical T and B lymphocytes in several respects. For example, they are unusually radioresistant, show no immunological memory, are present in thymectomized or congenitally athymic mice, are not functional until about 3 weeks after birth. These characteristics suggest that the effectors are natural killer (NK) cells. Although most of the evidence implicating NK cells in hybrid resistance is circumstantial, the experiments of Warner and Dennert are more direct in that they show that resistance can be restored to mice with a congenital or induced defect in NK activity by the infusion of cells belonging to an NK clone. Conversely, treatment of mice with an antibody to NK cells abrogated hybrid resistance to parental bone marrow grafts. Both NK cells and the effectors of hybrid resistance are generally considered to be nonspecific. We have now investigated this assumption by attempting to prevent hybrid resistance by neonatal tolerance induction with parental strain antigens. Our data indicate that hybrid resistance can be abrogated by this means and that the tolerance is specific and transferable with Thy-1+ spleen cells.
Animals↗