Levamisole (LMS), the levoisomer of 2,3,5,6-tetrahydro-6-phenylimidazo [2, l-b] thiazole hydrochloride, has demonstrated immunoenhancing activities on mouse responsiveness to antigenic stimuli (1-4). This activity depended upon T-cell potentiation as evidenced by increased gra~-versus-host reaction when donors were treated by LMS (5), by accelerated rejection of isogeneic skin grafts (6, 7), or by enhanced levels of delayed hypersensitivity in LMS-treated mice (7). Sodium diethyldithiocarbamate, DTC, a noncyclic sulphur drug, induced similar responses (8). LMS effect can be transferred by a serum factor obtained from animals after treatment with LMS. In transfer experiments, this factor enforced immune responses to sheep red cells (SRC) in recipient mice and induced regression of tumor size in leukemic AKR mice, even when leukemic mice have failed to respond to treatment with LMS (9, 10). On the other hand, the impaired development of T ceils in nu/nu mice has been ascribed to lack of the maturation stimulus, or stimuli, normally provided by thymus factors (11-15).In this report, we present evidences that LMS or DTC induce in vivo acquisition of specific T-cell markers by undifferentiated precursor lymphoid cells of thymusless nude mice and concomitantly induce functional immune activation. Also, that serum from treated nu/nu mice can transfer these in vivo activities and allow in vitro differentiation of precursor cells into T cells. Materials and MethodsHealthy nu/nu mice from the Edinburgh strain (16), obtained from the Centre de Sdlection des Animaux de Laboratoire (CNRS, Orldans, France), were maintained in an air-conditioned room and partially protected from environmental infections by Isocap filters (Iffa-Credo, l'Arbresle, France).LMS or DTC were dissolved in pyrogen-free saline and subcutaneously administered in vol of 0.2 mt, at the doses indicated in the individual experiments. Doses of the drug were expressed in milligrams of the salt per kilogram body weight.In in vivo assays, 5-to 6-wk-old female nu/nu mice were killed 4 days after a single drug administration. Any mouse showing evidence of liver disease (17) was discarded from the experiment. In vitro induction assays were performed for 2.5 h at 37°C in a humidified CO2 incubator in the absence or presence of LMS or DTC. Amounts of the drugs varied from 10 -s to 10 -~ mM/10 ~ lymphocytes per ml of medium. Expression ofT-cell antigens on the cell surface was tested on either in vitro or in vivo induced lymphocyte suspensions in the cytotoxicity assay (18), using Thy-l.2 and TL 1, 2, 3 antisera kindly provided by E. A. Boyse. Each cytotoxicity assay was performed in duplicate. Induction of an acquired functional (helper) activity was assayed on day 4 after immunization of nu/nu mice with SRC and simultaneous treatment with LMS or with DTC
Immunocompetence was evaluated in 36 untreated and noninfected patients affected with myelodysplastic syndromes (MDS). T-cell number and activity were evaluated by counts of total T-cells and T-lymphocyte subsets, and by measure of DNA synthesis in response to phytohemagglutinin and Concanavalin A. B-cells were evaluated as surface immunoglobulin- (SIg+) bearing cells and by serum immunoglobulin levels. Granulocyte activities were evaluated by responses to chemotaxis and to nitroblue tetrazolium test. Complement activity was measured by classic hemolytic complement assay. In addition, circulating immune complexes were detected in serum. MDS were associated with a significant decrease in the absolute numbers of total T (E-rosetting and T3+) cells, T4+, and T8+ cells and a dramatic decrease of the responses to Concanavalin A. An impairment of either chemotaxis or of nitroblue tetrazolium (NBT) test was frequently encountered. An increase in the levels of IgG or IgA was also a frequent feature. The findings reveal that all patients with a high degree of T-cell impairment have refractory anemia associated with an excess of medullary blast cells. All in all, the data suggest that the counts of the absolute number of cells bearing the T3 and T8 phenotypes could be of prognostic value: the higher the number, the better the patient's survival.
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