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Huntington's disease: delayed hypersensitivity in vitro to human central nervous system antigens.

Huntington's disease is a hereditary, chronic, degenerative disease of the brain which is transmitted by an autosomal dominant gene. We have discovered that lymphocytes from patients with Huntington's disease respond to the presence of brain tissue from patients with the disease by producing migration inhibition factor, a correlate of the cellular immune response. Lymphocytes from donors without the disease do not respond to the diseased brain tissue, and lymphocytes from patients with Huntington's disease respond only rarely to brain tissue from donors without the disease.

Adult↗

Delayed hypersensitivity in man: a correlate in vitro and transfer by an RNA extract.

The migration of sensitized human monocytic-phagocytic cells from lymph-node tissue-culture suspensions was regularly and specifically inhibited by purified protein derivative or histoplasmin. Moreover, when nonsensitive cells were incubated with an RNA extract from lymph nodes of donors sensitive to purified protein derivative, histoplasmin, or both, the migration of these cells was specifically inhibited by these antigens. Ribonuclease inactivated the RNA extract.

Culture Techniques↗

Delayed hypersensitivity in man: effects of systemic anticoagulation.

Skin test reactivity, lymphocyte transformation, and mononuclear cell tissue factor generation were evaluated both before and during systemic anticoagulation in 24 volunteers. Anticoagulation with warfarin decreased skin test induration and tissue factor generation, but lymphocyte trnasformation remained unchanged. An intact coagulation mechanism, including tissue factor generation, appears to be important for the development of skin test induration in humans.

Adult↗

In vivo studies on the cellular source of migration inhibitory factor in mice with delayed hypersensitivity.

Mice sensitized intravenously with 300 microgram of BCG cell walls in Drakeol-Tween 80 and challenged intravenously 3 weeks later with 50 mg of old tuberculin released migration inhibitory factor (MIF) into the circulating blood in quantities that could be detected in serum dilutions of 1:64 to 1:128. When thymus-derived lymphocytes (T-cells) were absent at the time of sensitization, as in neonatally thymectomized mice or in athymic nude mice, detectable amounts of MIF were not formed. Sensitized mice treated with either anti-theta serum or anti-bone marrow-derived lymphocyte (B-cell) serum before intravenous challenge with old tuberculin released reduced amounts of MIF into the circulation. Mice lethally irradiated, reconstituted with B-cells, sensitized with BCG cell walls, and then challenged intravenously 3 weeks later with old tuberculin did not release MIF into the circulation. When T-cells were injected at least 10 days before challenge, however, MIF appeared.

Animals↗

Delayed hypersensitivity responses of experimental animals to histoplasmin from the yeast and mycelial phases of Histoplasma capsulatum.

Controlled yeast lysate (CYL) and controlled mycelial lysate (CML) histoplasmins were produced from Histoplasma capsulatum grown in a nutritionally lean, chemically defined medium. The lysates were assayed for skin-test activity in guinea pigs sensitized by infection with the homologous organism. In some studies, nonliving vaccine preparations were employed also. Inter-lot biological variation was minimal, and 20 lots of the CYL reagent elicited strong dermal reactions with high specificity. Further, CYL reagents were nonreactive in guinea pigs infected with Coccidioides immitis, whereas the commercial Food and Drug Administration preparations cross-reacted to some degree. The CML histoplasmins were generally less reactive than the CYL preparations and exhibited somewhat more inter-lot variation in sensitivity and specificity. No correlation between potency and protein:polysaccharide ratios were observed with either reagent. An intradermal test with the CYL reagent did not induce significant changes in the complement-fixing titer of sensitized guinea pigs. Such changes in sensitized animals were elicited by a skin test with commercial histoplasmin.

Animals↗

Two new inhibitory activities in blood of mice with delayed hypersensitivity, after challenge with specific antigen.

In addition to the activities associated with migration inhibitory factor and type II interferon, two other inhibitory activities have been found in the sera of mice infected intravenously with BCG and 3 weeks later challenged intravenously with old tuberculin. Growth of three bacteria, Streptococcus faecalis, Staphylococcus aureus, Pseudomonas aeruginosa, and one yeast, Candida albicans, was inhibited in vitro by a factor or factors in the serum. Also, hematopoiesis of mouse bone marrow cells in a soft agar medium was suppressed by the serum.

Animals↗

Delayed hypersensitivity to heart antigens in Chagas' disease as measured by in vitro lymphocyte stimulation.

Reactivity to Trypanosoma cruzi antigens and autoreactivity to heart antigens were evaluated in 27 patients with Chagasic cardiomyopathy (group I), 52 patients without evidence of cardiac dysfunction (group II), and 36 selected controls, either healthy patients or patients with other heart diseases (group III). The in vitro lymphoblastogenesis response to T. cruzi antigens was found to be high in groups I and II and low in group III. The mean stimulation index to T. cruzi antigens, in fact, tended to be highest in group I, suggesting a more intense immune response in patients with Chagasic cardiomyopathy. The proportion of individuals with reactivity to heart antigens was 28.6% in group I, 25% in group II, and 0% in group III. The finding of an equal percentage of reactivity to heart antigens in groups I and II was unexpected, as a higher incidence of positive reactions in group I was predicted. Consequently, it is thought that this finding and its relevance to the pathogenic process of Chagasic cardiomyopathy need to be carefully assessed in a longitudinal study.

Adult↗

Agar microdroplet assay for delayed hypersensitivity to Legionella pneumophila serogroup 1.

An agarose microdroplet technique was utilized to assess the cellular immunity of guinea pig lymphoid cells to Legionella pneumophila antigen in vitro. Both direct and indirect migration inhibition procedures were shown to be capable of detecting sensitization of guinea pigs to L. pneumophila antigens. Animals injected with adjuvant alone or unrelated antigens did not yield spleen cells responsive to L. pneumophila, indicating the specificity of the response. Migration inhibition factor induction by Legionella antigen in vitro correlated well with skin test responses in vivo. The positive reaction detected by migration inhibition occurred at times similar to that of skin reactivity but later than that of the earliest serum antibody titers. The assay appears to be useful for monitoring sensitization to Legionella and may be applicable to the study of cell-mediated immunity to this bacterium in infected individuals.

Animals↗