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Lead has been shown to exert toxic effects during early development. In these in vivo and ex vivo experiments, the effect of lead on the immune system of the developing embryo was assessed. Nine-week-old female Fischer 344 rats were exposed to lead acetate (0, 100, 250, and 500 ppm lead) in their drinking water during breeding and pregnancy (exposure was discontinued at parturition). Offspring received no additional lead treatment after birth. Immune function was assessed in female offspring at 13 weeks of age. Dams in lead-exposed groups were not different from controls with respect to the immune endpoints used in these experiments; however, in the offspring, lead modulated important immune parameters at modest exposure levels. Macrophage cytokine and effector function properties (tumor necrosis factor-alpha and nitric oxide production) were elevated in the 250 ppm group, while cell-mediated immune function was depressed, as shown by a decrease in delayed-type hypersensitivity reactions in the 250 ppm group. Interferon-gamma levels were decreased in the 500 ppm treatment group. Serum levels of IgE were increased in rats exposed to 100 ppm lead. These results indicate that exposure of mothers to moderate levels of lead produces chronic immune modulation in their F344 rat offspring exposed in utero. Since the mothers were not susceptible to chronic immune alterations, a developmental bias to the immunotoxic effects of lead is indicated. The differences observed are consistent with the possibility that lead may bias T helper subset development and/or function, resulting in alterations in the balance among type 1 and type 2 immune responses.

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SUMMARYThe reactivities of peroxidase-labelled concanavalin A (con A: 20 jug/ ml) with sections from various avian lymphoid organs were compared. With chicken bursae, con A binding and subsequent differential staining detected a non-lymphoid leukocyte population distributed throughout the sections. A comparable population was not observed in sections from the gland of Harder. With free cells, con A at low concentrations was found to selectively bind to both macrophages and heterophils but not to lymphocytes. Flow cytometric analysis with fluorescein isothiocyanate-labelled con A . also confirmed this selective binding.Peroxidase-labelled con A was used to detect non-lymphoid leukocytes present in areas of metastasised tumours in tissues of quail-chicken hybrids. Such staining was not seen in comparable normal tissues. Evidence that the tumour-localised leukocytes were macrophages was shown by the reactivity of these cells with a monoclonal anti-chicken la antibody.

Feulgen-Rossenbeck staining of lymphoid cells of quail-chicken hybrids in histologic sections revealed a pattern of heterochromatin arrangement distinguishable from that of either parental type. During interphase, hybrid lymphocytes exhibited combined characteristics of both the parental quail and the parental chicken. Hybrid heterochromatin was arranged in a large central mass as in the quail and in fairly evenly distributed small chromacenters around the periphery of the nucleus similar to the arrangement in the chicken. It is suggested that this pattern of staining can be used as a marker for hybrid cells in studies of genetic interactions.