The objective of this research was to determine whether gram-negative bacteria frequently isolated from periodontally diseased sites contained polyclonal B-cell activators. Polyclonal B-cell activation, which results in nonspecific activation of multiple B-cell clones, was analyzed by a hemolysis-in-gel assay designed to detect a broad range of antibody specificities. Extracts from numerous bacterial strains, including Bacteroides gingivalis, Bacteroides melaninogenicus subsp. melaninogenicus, B. metaninogenicus subsp. internedius, Fusobacterium nucleatum, Selenomonas sputigena, Capnocytophaga ochracea, and Actinobacillus actinomycetemcomitans, were tested. Extracts of the above organisms were found to stimulate polyclonal antibody responses in cultures ofnormal human peripheral blood lymphocytes, although the magnitude of stimulation varied among the extracts. Optimal antibody-forming cell responses were found at stimulator doses between 5 and 1,000 ,tg/ml. We conclude that the resident gram-negative subgingival flora associated with periodontal lesions possesses potent polyclonal B-cell activators. These activators may contribute to disease pathogenesis by inducing B lymphocytes to produce antibody, osteolytic factors, or both and possibly other mediators of inflammation.
These studies were designed to examine the role of regulatory T cells in the polyclonal antibody response of human peripheral blood lymphocytes to extracts of bacterial isolates commonly associated with periodontal disease. Polyclonal antibody responses to the organisms tested were found to be T cell dependent, as are most of the B-cell activators in the human system. Functional T helper activity was resistant to 1,500 rads of irradiation. Optimal polyclonal antibody responses to the bacterial extracts occurred at a 3:1 T-cell-to-B-cell ratio, whereas pokeweed mitogen-induced responses peaked at a 1:1 ratio, suggesting a difference in T-cell regulatory influences in response to these activators. Purified populations of T helper and suppressor cells exerted potent regulatory control of the responses to the bacterial extracts. These findings support the conclusion that regulatory T lymphocytes exert a potent modulating influence over the polyclonal response to periodontally associated bacteria and may play an important role in regulating the lymphocyte response in the diseased site.
Blood plasma from cows treated with somidobove, a form of recombinant bovine somatotropin, was assayed for development of antibodies against the protein. Forty-three Holstein cows, selected from an animal safety study, were monitored. Cows were divided into four groups and treated with placebo, 960, 2880, or 4800 mg somidobove per dose at 28-d intervals during two successive lactation periods. Blood plasma was collected at intervals prior to and during the lactations, and levels of IgG antibody reactive with somidobove were determined in an enzyme-linked immunosorbent assay. Virtually all of the cows treated with somidobove developed low levels (less than 40 micrograms/ml) of antibody against somidobove. One or two cows from each group responded with some-what higher levels, ranging from 40 to 200 micrograms/ml. Responses generally increased during the first 3 mo of treatment, then decreased, and remained constant with continued treatment. There was no sign of a memory response within or among the lactation periods, and no adverse health effects or decreases in lactational performance were associated with antibody production.
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