Hyporesponsiveness of Canine Bronchoalveolar Lymphocytes to Mitogens: Inhibition of Lymphocyte Proliferation by Alveolar Macrophages

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Abstract
Unfractionated canine bronchoalveolar cells (65% macrophages, 26% lymphocytes, and 9% granulocytes) obtained by lavage were markedly hyporesponsive to stimulation with concanavalin A, phytohemagglutinin, or pokeweed mitogen. The mechanisms responsible for the lack of responsiveness of bronchoalveolar lymphocytes were investigated. Unfractionated bronchoalveolar cells were depleted of adherent cells by sequential adsorption on plastic (nonadherent cells) and by nylon wool filtration (column-purified cells). Nonadherent and column-purified cells were substantially depleted of macrophages, enriched for lymphocytes, and displayed marked increases in their responses to mitogens (up to 7-fold). Preparations of unfractionated bronchoalveolar cells markedly suppressed the responses of blood lymphocytes to mitogens; nonadherent and column-purified cells displayed minimal suppressive activity. Plastic-adherent cells, prepared from unfractionated bronchoalveolar cells, contained up to 93% macrophages and these adherent cells were potent suppressors of mitogen-responses when co-cultured with blood lymphocytes. Suppressor activity of adherent cells was radioresistant and was reversed by the addition to cultures of low concentrations of indomethacin. The data indicate that alveolar macrophages are the adherent cells responsible for this suppressor activity. The responses of nonadherent and column-purified bronchoalveolar lymphocytes, although substantially greater than those of equal numbers of unfractionated bronchoalveolar lymphocytes, were consistently less than 25% of the responses of similarly prepared blood lymphocytes. Differences in cell viability between blood and lung lymphocytes were not found. Neither the addition of indomethacin nor the addition of mitomycintreated blood mononuclear cells increased the responses of column-purified bronchoalveolar lymphocytes. Our studies demonstrate two mechanisms that limit the responses of canine lung lymphocytes to mitogenic stimulation: a suppression by alveolar macrophages of lymphocyte proliferation and an inherent hyporesponsiveness of bronchoalveolar lymphocytes. These may be of importance in regulating the response of lung to inhaled antigens.