Prevention of antigen-induced bronchial hyperreactivity and airway inflammation in sensitized guinea-pigs by tacrolimus

We examined the effect of the immunosuppressive agent, tacrolimus (FK506), on antigen-induced bronchial hyperreactivity to acetylcholine and leukocyte infiltration into the airways of ovalbumin-challenged guinea-pigs. Subcutaneous injection of 0.5 mg/kg of FK506, 1 h before and 5 h after intra-nasal antigen challenge prevented bronchial hyperreactivity to aerosolized acetylcholine, eosinophilia in bronchoalveolar lavage (BAL) fluid and bronchial tissue and the invasion of the bronchial wall by CD4+ T-lymphocytes. FK506 also suppressed ovalbumin-induced increase in the number of leukocytes adhering to the pulmonary vascular endothelium and expressing alpha4-integrins. Inhibition by FK506 of antigen-induced bronchial hyperreactivity in sensitized guinea-pigs may thus relate to its ability to prevent the emergence of important inflammatory components of airway inflammation, such as eosinophil accumulation, as well as CD4+ T-lymphocyte infiltration into the bronchial tissue.     

Delayed cutaneous hypersensitivity response in tetanus toxoid sensitized rhesus monkeys: predictor of anergy and value in tuberculin skin testing

The primary problem in using the tuberculin skin test in nonhuman primates is the clinical uncertainty concerning the animal's ability to elicit a delayed cutaneous hypersensitivity response. A negative tuberculin skin test can only be meaningful if the animal can produce a delayed cutaneous hypersensitivity reaction. Veterinarians deliberately sensitize animals to antigens in the form of prophylactic vaccination. Therefore, if nonhuman primates were deliberately sensitized to an antigen capable of producing a hypersensitivity response, that antigen should serve as a positive control for delayed cutaneous hypersensitivity reactions. Tetanus toxoid was chosen because repeated immunizations with this antigen is recommended routine medical practice for nonhuman primates housed outdoors. Twenty juvenile, male rhesus (Macaca mulatta) monkeys were selected for this study. The monkeys were assigned randomly to one of two groups of ten animals. The test group was vaccinated with tetanus toxoid intramuscularly at 1 month intervals for a total of three vaccinations. The control group was treated the same except saline was administered rather than tetanus toxoid. Following sensitization, the two groups of animals were challenged with tetanus toxoid intradermally. Eight of the ten monkeys in the test group responded to the tetanus toxoid while none of the control groups responded to the tetanus toxoid. Elicitation of a delayed cutaneous response in animals sensitized to tetanus antigen before challenge may serve as a positive control for delayed cutaneous hypersensitivity. This simple test may serve as a useful adjunct in making objective clinical decisions concerning anergy-suspect animals.     

Comparison of TRF, propranolol-glucagon, insulin and glucose stimulation tests in acromegaly.

In 7 acromegalic patients growth hormone responses were studied following administration of synthetic TRF, propranolol-glucagon, insulin, and glucose p.o. Except for the glucose tolerance test, a good reproducibility of the STH response was observed. In 5 out of the 7 patients, there was a distinct rise in the plasma STH level after TRF. All patients with a positive insulin tolerance test responded to TRF, as did the two late responders to glucagon; the early responder to the latter test did not respond to TRF. It has been suggested (Liuzzi et al. 1974a) that TRF might be used as a screening test for detecting hypothalamic dependency of the acromegaly. This study suggests that further study is required before accepting this hypothesis and that a response to a combination of tests (TRF, glucagon, insulin) might be a better screening method.     

Maintenance of lymphocyte surface Ig by mitogen stimulation in vitro.

In 4 to 24 hr cultures of rabbit lymphoid cells in medium supplemented with autologous serum, most B cells lost their surface Ig as assayed by rosette formation with anti-Ig antibody-coated erythrocytes. This loss was prevented by adding selected mitogens such as streptococcal mitogen (SM), lipopolysaccharide, and concanavalin A or by supplementing the medium with fetal calf serum. When SM was added at various times to the cultures (1, 2, 3, and 4 hr), it was effective in maintaining the approximate level of Ig-bearing cells present at the time of its addition but was ineffective in restoring the level of Ig-bearing cells present at the time the cultures were intiated. Very small, submitogenic doses of SM were sufficient to maintain the level of Ig-bearing cells. The data suggest that lymphocytes require continuous stimulation to maintain their surface receptors.     

Effect of different immunization and challenge procedures on in vivo tumor immunogenicity tests

Summary Three different methods of immunization and two methods of challenge were used to test a series of methylcholanthrene (MCA)-induced sarcomas for their immunogenicities in vivo. Although there was some variation in the degree of immunity produced, similar results were obtained with the three immunization procedures. Challenge with explants of tumor tissue was found to be as sensitive a measurement of the antitumor response as challenge with a single cell suspension. The results indicate that in a substantial series of tumors, the relative immunogenicities are characteristics of the tumors themselves and not artifacts due to the immunization or challenge procedures used.Abbreviations used: EDTA, ethylenediamine tetra acetic acid; HBSS, Hank's Balanced Salt Solution; IR, Immunogenicity Ratio; MCA, 3-methylcholanthrene; mito-c, mitomycin c; r_s, Spearman Rank correlation coefficient; SC, subcutaneous; WBI, whole-body irradiation     

Comparison of the tine and Mantoux tuberculin tests. Report of the Tuberculin Subcommittee of the Researched Committee of the British Thoracic Association.

Intracutaneous (Mantoux 5 TU) and tine tuberculin tests were performed on the opposite arms of 307 people. The results of each test were read by two independent observers at either 48 or 72 hours. Positive readings were recorded in 59% of the Mantoux tests; induration was 10 mm or more in 34.7% of cases. Positive readings were recorded for 3.9% of the tine tests, and a further 15.5% were recorded in the doubtful category. The tine test is unsuitable for epidemiological use because of the high proportion of negative and doubtful results in people positive on the Mantoux test. For the same reasons its usefulness in clinical practice is very limited.     

Effect of controlled antigenic stimulation on lymphocyte subsets in pigs and pig fetuses

The effect of controlled antigenic stimulation in immunologically virgin organisms,i.e. pig fetuses treated with NDCM (Nocardia delipidated cell mitogen) and germ-free (GF) piglets associated with a non-pathogenicE. coli O86, on peripheral blood lymphocyte subsets defined by the expression of CD5 and CD8 was studied by double color flow cytometry. Stimulation of both fetuses and GF piglets increased the frequency of CD8^low+ lymphocytes. A prominent subset of CD5⁻ CD8^low+ NK cells was present in GF andE. coli associated piglets and their frequency was slightly higher inE. coli associated animals. The most pronounced difference between stimulated and non-stimulated animals was in a relative proportion of an ill-defined lymphocyte subset with an unusual CD5^low+ CD8^low+ expression. Both NDCM injection into fetal blood circulation and association of GF piglets withE. coli resulted in a marked increase of frequency of CD5^low+ CD8^low+ lymphocytes in peripheral blood.     

Short-term stimulation of lymphocyte proliferation by indomethacin in vitro and in vivo

The effect of short-term (up to 24 h) in vitro and in vivo treatment with indomethacin was studied on the blastogenesis of mouse spleen cells. Indomethacin in itself induced a strong proliferation of the lymphocytes starting after 6 h treatment both in vitro and in vivo. Besides, significantly enhanced the blastogenesis of splenocytes in response to various doses of PHA and Con A. The stimulation of lectin-induced lymphocyte proliferation occurred after indomethacin treatment both in vitro and in vivo. Indomethacin had no major effect on the distribution of Lyt-1+ and Lyt-2+ subsets within the spleen cell population. An important role of the prostaglandins in the early phase of lymphocyte activation is suggested.     

Effect of stimulation of dopamine and histamine receptors on spontaneous lymphocyte adhesion in vitro

With the help of spontaneous lymphocyte adhesion test the influence of dopamine and histamine on the adhesion of peripheral blood lymphocytes has been studied in healthy donors. It was shown that dopamine enhanced spontaneous lymphocyte adhesion, with the optimal concentrations of the substance for the realization of a stimulating effect being 10(-4)-10(-6) M. The effect of the enhancement was pharmacologically specific, as it was completely blocked by dopamine receptor-blocker--haloperidol. It was demonstrated that low concentrations of histamine (10(-7)-10(-8) M) enhanced, while higher concentrations (10(-6)-10(-3) M) inhibited lymphocyte adhesion. Dimedrol, but not cimetidine abolished the enhancement of spontaneous lymphocyte adhesion, while the adhesion inhibition was blocked by cimetidine, but not dimedrol. Thus, the revealed histaminergic enhancement and inhibition of spontaneous lymphocyte adhesion is mediated through the influence of histamine on H1- and H2-receptors, respectively.