IMMUNOGLOBULIN-LEVELS IN MICE UNDERGOING GRAFT-VERSUS-HOST REACTION.
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Biomedical subjects
Publications and source records attributed to B G ARNASON.
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Rats thymectomized at birth gained weight and otherwise developed normally, but were found to be very susceptible to intercurrent infections. Both Arthus reactivity and delayed hypersensitivity to BSA were markedly impaired in rats thymectomized during the first week of life and significantly impaired in rats thymectomized as late as 3 weeks after birth. The inhibition of Arthus reactivity in thymectomized rats was well correlated with their failure to develop significant titers of precipitating or hemagglutinating antibody. However, natural heteroagglutinin titers were not altered in these animals, and no abnormality of serum proteins, including gamma-globulin could be detected by paper electrophoresis. The loss of immunologic activity could not be corrected by injecting homogenates of spleen or thymus before and during the sensitization period. Splenectomy at birth did not influence Arthus or delayed reactivity.
In rats thymectomized at birth and tested in adult life, ability to develop autoallergic encephalomyelitis was completely suppressed, there was a marked diminution in the degree of tuberculin sensitization appearing after a single injection of mycobacteria in oil, rejection of skin homografts was markedly delayed, and adjuvant arthritis was not appreciably affected. At the same time there was a striking decrease in the circulating level of small lymphocytes.
In rats thymectomized at birth, there was a profound depletion of small lymphocytes in various lymphatic organs. In the spleen, these cells were completely lacking from the Malpighian bodies and splenic white pulp. Empty reticular structures remained surrounding the white pulp arterioles. In the lymph nodes, large masses and nodules of small lymphocytes (primary lymphoid nodules) were either markedly depleted or absent, as were the zones of these cells normally surrounding germinal centers. In both spleen and nodes, germinal centers appeared normal in size, number, and cellular make-up; and plasma cells were found in normal or even increased number in their customary position. Rats which in spite of thymectomy developed intense Arthus or delayed reactivity showed incomplete depletion of the lymphoid tissue. It is concluded that small lymphocytes of the spleen and lymph nodes may come, in large part, directly from the thymus and are not derived from medium and large lymphocytes of the germinal centers. It is suggested that there may be a second population of small lymphocytes whose function is unrelated to the thymus lymphocytes.
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Rabbit antisera against normal guinea pig lymph node, when injected into guinea pigs, produced transient depression of the level of blood lymphocytes. It had no effect on other circulating cellular elements. Repeated injection over several days produced lymphopenia, which became progressively less marked with continued treatment, and clear-cut depletion of small lymphocytes in lymph nodes, whether draining an inoculation site or remote. In guinea pigs treated with lymphocyte antiserum, there was marked suppression of the tuberculin and contact allergic reactions and the "delayed" skin reaction to purified diphtheria toxoid, and a relative suppression of allergic encephalomyelitis and the rejection of first set skin homografts. There was a slight effect on second set graft rejection and no effect on PCA or the reversed passive Arthus reaction. Non-specific reactions to intradermal turpentine or to concentrated dinitrochlorobenzene placed on the skin were moderately reduced. The suppression of these reactions (except allergic encephalomyelitis) was closely correlated with the degree of lymphopenia. Lymphocyte antiserum absorbed with normal blood white cells lost both its lymphopenic effect and its ability to suppress the tuberculin reaction. It is tentatively concluded that a circulating mononuclear cell, probably the small lymphocyte, is the primary reactant in the various types of delayed hypersensitive reactions.