Spontaneous and antibody-dependent cell-mediated cytotoxicity by human T cell subpopulations.

Human peripheral blood non-T cells, T cells and their subpopulations (Tmu, Tgamma, Tphi, Tgamma-depleted cells, and Tmu-depleted cells) were assayed for their capacity to mediated spontaneous lymphocyte-mediated cytotoxicity (SLMC) or natural killer activity against K562 tumor cell line and antibody-dependent cellular cytotoxicity (ADCC) against chicken erythrocytes coated with antibody. Non-T cells, unseparated T cells, Tgamma cells, and Tmu-depleted (Tgamma-enriched) cells were found to have both SLMC (NK activity) and ADCC. Tmu, Tphi, and Tgamma-depleted cells had minimal or no SLMC and ADCC activity. This study demonstrates that SLMC and ADCC activity in T cells is mediated by Tgamma cell subpopulations. These two cytotoxic reactions were either mediated by two distinct subsets of Tgamma cells or by a single effector cell using two different mechanisms.     

Two decades of experience with testicular tumors in children at St Jude Children's Research Hospital

From 1968 to 1988, 24 children and adolescents with malignant testicular tumors were treated at St Jude Children's Research Hospital. Pure yolk sac tumors (YST) were present in 13 cases; 11 patients had other types of nonseminomatous malignant germ cell tumors. Children with localized and totally resectable disease (stage I) were treated by orchiectomy alone; all others also received chemotherapy. Five of ten patients treated before the implementation of a multiagent chemotherapy protocol in 1979 have died. By contrast, all of the 14 patients treated on this protocol are alive. The improved survival during the past decade is attributable to better diagnostic imaging techniques, the availability of serum tumor markers to monitor disease activity, and more effective chemotherapy. Orchiectomy alone is sufficient treatment for patients with clinical stage I disease who show appropriate reductions in tumor marker levels after surgery. Modern platinum-based chemotherapy provides disease control in patients with higher stage disease.     

Immunological memory induced by genetically transduced tumor cells

Background: Recent studies have demonstrated the usefulness of gene-modified tumor cells for immunotherapy. Using the tumorigenic murine fibrosarcoma, MCA 106, we investigated the effects of localized interferon-γ (IFNg) secretion on tumorigenicity and on long-term memory. Methods: The murine IFNg (MuIFNg) gene was introduced into tumor cells. High and low IFNg-secreting clones were isolated. C57BL/6 mice were injected subcutaneously (s.c.) with either parental (P), high or low IFNg-secreting (H- or L-IFNg) cells, and tumor growth was assessed weekly. Spleens were harvested on different days postinjection (p.i.) to assess in vitro cytolytic activity. In parallel, tissues from injection sites were stained with macrophage-, CD4-, and CD8-detecting antibodies. Mice were injected s.c. with H-IFNg MCA106 tumor. After 150 days the animals were rechallenged s.c. with MCA106P in one leg and with irrelevant syngeneic tumor in the other. Results: Both P- and L-IFNg cells had similar growth, whereas the H-IFNg cells never grew. Only splenocytes from the H-IFNg animals showed in vitro CTL activity persisting until day 30 p.i. Histological data revealed a macrophage and CD4⁺ infiltrate much earlier in the H-IFNg group compared with the P group. Only the irrelevant, syngeneic tumor grew in animals previously injected with H-IFNg cells, whereas both P and irrelevant syngeneic tumors grew in controls. Conclusions: Transduction of MCA106 cells with the MuIFNg gene diminished in vivo tumorigenicity in proportion to the amount of IFNg secreted. Immunization with H-IFNg cells elicited a host response characterized by macrophages and CD4⁺ cells. Long-term tumor-specific memory was seen after immunization with H-IFNg cells.     

Beta-adrenoceptor desensitization in guinea-pig isolated trachea

Exposure to (-)-isoprenaline (25 microM, 1 h) caused a stereoselective, time and concentration-related decrease in smooth muscle beta 2-adrenoceptor function in guinea-pig trachea. Furthermore, tracheal relaxant responsiveness to the beta-adrenoceptor agonists (+/-)-fenoterol and (-)-noradrenaline was reduced, while that to theophylline and nitroprusside was unaffected. Responsiveness to forskolin was marginally but significantly reduced. Indomethacin, a cyclooxygenase inhibitor and mepacrine, an inhibitor of phospholipid turnover, had no significant effect on the extent of isoprenaline-induced desensitization. Conversely, cortisol (25 microM) significantly reduced desensitization and enhanced the rate of spontaneous recovery of responsiveness to isoprenaline. Desensitization was not accompanied by a reduction in the density of beta-adrenoceptors in the trachea, as assessed by binding and light microscopic autoradiography using [125I]iodocyanopindolol [( 125I]CYP). Thus, desensitization was probably caused primarily by beta-adrenoceptor/adenyl cyclase uncoupling. This model may be useful in investigations of the effect of glucocorticoids on the beta-adrenoceptor dysfunction recognized in severe asthma.     

Alterations in immunological reactivity in encephalomyocarditis virus-induced murine diabetes. I. Defective primary IgM plaque forming cell responses to sheep erythrocytes: correction by islet cell transplantation.

Increasing data suggest a possible viral aetiology of juvenile onset, insulin-dependent diabetes mellitus. The M variant of the encephalomyocarditis (EMC) virus infects murine pancreatic beta cells and causes a diabetes like syndrome in susceptible strains of mice. Abnormalities in immunological function have been documented in patients with diabetes mellitus and in spontaneous, streptozotocin-induced and alloxan-induced diabetes in animals. The present study documents a significant impairment of the ability of mice with EMC virus (M variant)-induced diabetes to generate a direct, IgM PFC response after in vivo immunization with sheep erythrocytes. This abnormality appears to be a direct consequence of the diabetic state and not EMC virus infection, per se, since mice infected with EMC virus that do not become diabetic have normal direct PFC responses and islet cell transplantation, which cures the diabetes, corrects the defect in PFC responsiveness.     

Long survival and immunologic reconstitution following transplantation with syngeneic or allogeneic fetal liver and neonatal spleen cells.

(1)Spleen cells from newborn syngeneic and allogeneic mice that lack fully differentiated T lymphocytes can be used as a hematopoietic source to reconstitute both hematopoietic and lymphoid systems of lethally irradiated mice without producing a GVHR. (2) Fetal liver cells from syngeneic and allogeneic mice that lack postthymic T lymphocytes can also be used for hematopoietic and immunologic reconstitution of lethally irradiated mice without producing GVHR. (3) Immunologic deficiency is observed in some experiments in mice given supralethal irradiation (1000 R) and fetal liver as reconstituting hematopoietic tissue. (4) The findings suggest that Tcells, at an early stage of differentiation, are more susceptible to tolerance induction than are T lymphocytes at later stages of differentiation and do not, in general, produce GVHR. (5) It is postulated that hematopoietic cells, free of postthymic lymphoid cells, can be used for hematopoietic or immunologic reconstituting and cellular engineering without producing GVHD.     

Complex carbohydrates in the dietary management of patients with glycogenosis caused by glucose-6-phosphatase deficiency

Carbohydrates with digestion characteristics between those of lente uncooked starches and rapidly digestible oligosaccharides were administered in a dose of 1.5 g/kg body weight to five patients with glycogenosis from glucose-6-phosphatase deficiency. Postprandial duration of normoglycemia and concentrations of blood insulin and lactate were determined. Uncooked barley groats in water, or incorporated in a meal turned out to behave as lente carbohydrates. Uncooked couscous in water, couscous incorporated in a meal, and partially cooked macaroni given as a meal behaved as semilente carbohydrates as compared with uncooked cornstarch and glucose. The in vitro determination of the digestibility index along with the in vivo tolerance test enables us to choose and incorporate semilente carbohydrates in the day-time treatment of patients.