Cytolytic activity of pulmonary and systemic lymphoid cells from C57BL/6 mice following intrapulmonary or intraperitoneal immunization with allogeneic tumor cells

In order to demonstrate whether specific cytotoxic T cells could be induced in lung parenchyma, C57BL/6 mice were immunized by the intrapulmonary route with allogenetic tumor cells (P815). Ten days after administration of 20 x 10(6) allogeneic cells, peak concentrations of cytotoxic cells were found in lung, tracheobronchial lymph node, and spleen. With reduction in immunizing dose, lytic activity disappeared from spleen and lymph node, but persisted in lung. The cytolytic activity was specific for the immunizing alloantigen, was abolished by antitheta serum, and could not be attributed to macrophages. For comparison, C57BL/6 mice were immunized by the intraperitoneal route with 20 x 10(6) P815 cells. The expected cytolytic activity was found in spleen and lymph nodes: however, unexpectedly high levels of cytolytic activity were also found in pulmonary lymphocytes. This activity was confirmed using a wide range of effector to largest cell ratios in the assay system. Quantitative cytolytic assays demonstrated that the maximum rate of cytolysis by pulmonary lymphocytes obtained from mice immunized intraperitoneally exceeded by 10- to 20-fold the rate of cytolysis by pulmonary lymphocytes obtained from mice receiving intrapulmonary immunization. These data demonstrate that cytolytic T-lymphocytes appear in lung parenchyma after either intrapulmonary or intraperitoneal immunization and that the intraperitoneal route is far more efficient than the intrapulmonary route. This cell-mediated immune mechanism potentially is available for host defense of respiratory tissue.     

Hydroxyurea (HU) in experimental hematology. II. Similarities and dissimilarities between HU and 3H-thymidine killing

The lethal effects of hydroxyurea (HU) and 3H-thymidine (3H-dT) on mouse hematopoietic cells were compared after various experimental procedures. The aim was to explore the relative efficiency of these two methods in analyzing the kinetic properties of progenitor cells. Both methods indicated that 40-50% of progenitor cells assayed with diffusion chamber culture (DCPC) were in S phase 3 days after cyclophosphamide treatment. Effects of HU, but not 3H-dT, were altered by neostigmine triggering of normal DCPC into cell cycle. On the other hand, cooling marrow cells before exposure to HU or 3H-dT largely abrogated the effect of HU, but not of 3H-dT. Blood-borne DCPC were not in cycle according to the HU effect. Separated blood DCPC were apparently in cycle, as judged with 3H-dT, but the Isopaque-Ficoll separation procedure rendered normal marrow DCPC susceptible to 3H-dT killing. When marrow cells were cultured in DC the HU technique appeared to be suitable for evaluation of modulation of progenitor cell (CFU-S or CFU-C) proliferation, whereas our previous experiments have shown that the 3H-dT technique is a convenient method to assess the initial triggering of CFU-S into cycle in DC culture.     

Effect of human leukocyte interferon on hepatitis B virus infection in patients with chronic active hepatitis

Four patients with chronic hepatitis B infection and chronic active hepatitis were treated with human leukocyte interferon. Three of them had consistently elevated levels of circulating Dane-particle markers, including Dane-particle-associated DNA polymerase activity, hepatitis B core antigen and Dane-particle-associated DNA. Parenteral interferon administration at a dosage between 6.0 X 10(3) and 17 X 10(4) U per kilogram per day was associated with a rapid and reproducible fall in all Dane-particle markers in the three patients. The suppressive effect was transient when the interferon was given for 10 days or less but appeared to be more permanent when administration was prolonged for a month or more. In addition, long-term interferon therapy was associated with a marked fall in hepatitis B surface antigen in two of three patients and a disappearance of e antigen in two of two patients. Interferon may be useful in limiting carrier infectivity or eradicating chronic infection.