SUPPRESSION OF EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS BY ANTIMETABOLITIES.
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Biomedical subjects
Publications and source records attributed to M W BRANDRISS.
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Some characteristics of inhibition of cell migration induced in tissue culture by the addition of specific antigen were studied. The following characteristics were found to be shared by this type of cellular hypersensitivity and delayed cutaneous sensitivity: 1. Specificity for the carrier moiety of haptene protein conjugates. The picryl protein conjugate used to sensitize guinea pigs inhibited migration of monocytic cells from these animals. Other picrylated proteins produced little inhibition. 2. Enhancement by mycobacterial adjuvants. Incorporation of tubercle bacilli with picrylated proteins in adjuvant-antigen emulsions stimulated the development of this cellular hypersensitivity to antigen. 3. Independence of circulating antibody. In contrast to cellular hypersensitivity, serum antibody (a) reacted with any of a number of picrylated proteins, (b) developed well in the absence of mycobacterial adjuvant, and (c) persisted in unchanged titer for 5 weeks in animals sensitized with saline solutions of antigen. During this time cellular hypersensitivity decreased remarkably. The in vitro system described provides a direct method to measure cell-antigen interaction and permits study of an aspect of the immune response not mediated by humoral antibody. The relation of cellular hypersensitivity to antibody formation and delayed hypersensitivity is discussed.
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Methotrexate inhibited the production of allergic encephalomyelitis in guinea pigs when administered between the time of sensitization and the onset of disease. If treatment was delayed until the day of onset of encephalomyelitis, the disease was still suppressed and the death rate was reduced. The protective effect of methotrexate was reversed by folinic acid.
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Guinea pigs with delayed hypersensitivity to protein antigens show a specific febrile response accompanied by a lymphopenia following injection of a desensitizing dose of specific antigen. No signs of shock are observed in highly sensitive animals following this injection. The response is not prevented in sensitive guinea pigs by inducing endotoxin tolerance or by pretreating with cortisone before specific challenge. Using a suitable antigen in sufficiently sensitive animals as little as 100 microg. can elicit a pronounced febrile response. Injection of a desensitizing dose of antigen specifically abolishes systemic as well as skin reactivity for several days. Normal or hypersensitive (delayed-type) animals passively sensitized with sufficient amounts of serum antibody show hypothermia after specific challenge and may show a delayed type of fatal shock. Differences were noted between their systemic reactivities, however, and the reactivity seen in specifically challenged tuberculous animals.