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Salivary gland dysfunction is a common sequela of the bone marrow transplantation procedure. We determined the effect of different bone marrow transplantation protocols on parotid salivary flow rate. Salivary secretion was substantially reduced during conditioning of all the recipients. A gradual flow rate reconstitution could be detected as soon as a few days after the bone marrow transplantation. Eight patients conditioned with total lymph node irradiation and chemotherapy or chemotherapy alone displayed earlier and complete recovery of saliva secretions 2 to 5 months after the grafting. Recovery was delayed and incomplete when total body irradiation was added to the conditioning regimen (seven patients). Six of these patients also developed graft-versus-host disease. The results suggest that total body irradiation induces irreversible damage to the parotid glands resulting in profound xerostomia followed by opportunistic infections. Chemotherapy with or without total lymph node irradiation does not induce such damage.

Radiation leukemia virus (RadLV)-induced preleukemic (PL) latency is characterized by the appearance of virus-infected PL cells in the thymus. The survival of these PL cells is dependent upon autostimulation with interleukin 4 (IL-4). We have intervened prophylactically in RadLV-induced preleukemia by using cyclosporin-A (CSA), which inhibits IL-4 production, and an immunotoxin (ITx) that kills PL cells. CSA efficiently inhibited IL-4 secretion from RadLV-induced PL and leukemic cells, and its administration to PL mice caused a significant delay in their death. An ITx consisting of anti-RadLV glycoprotein-70 (gp70) antibody coupled to ricin A chain efficiently inhibited protein synthesis in virus-infected cells in vitro and, when injected into PL mice, also delayed their death. Combined treatment with CSA and ITx prevented 75% of the treated PL mice from developing lymphoma. These results show that the development of malignancy from a premalignant state can be averted by a combination of therapeutic modalities that decrease the size and growth rate of the premalignant cell population.

Lymphocyte-mediated lysis of cells of the Raji, Daudi, Jijoye, and Bjab lines was elevated when fresh human serum was added to the assay. A higher proportion of effector-target conjugates was observed in the presence of human serum. In similar experiments lysis of 1301, Rael, and P3HR-1 cells was unaltered. All cell lines activated the alternative pathway of complement but they varied in the expression of receptors for complement component 3 (C3) and in the ability to fix the C3 cleavage products on their membrane. The enhancement of lysis in the presence of human serum occurred only with those cells that bound C3. This characteristic was correlated to the expression of C3 receptors. Analysis of the nature of the deposited C3 was performed with Raji cells. Raji cells exposed to human serum bound C3b as indicated by the immunoadherence test. The C3b was further processed to C3bi, because the immunoadherence declined with time and conjugate formation increased with Daudi cells, which carry the C3 receptors CR2 and CR3. This suggests that in the lytic assay lymphocytes with C3bi receptors are recruited in the presence of human serum. We assume that the bridge of C3 molecules between targets and effectors increases the avidity of their interaction.

Adult C57BL/6 mice exposed to fractionated irradiation or inoculated with the radiation leukemia virus (RadLV), develop high incidence (80-100%) of lymphatic leukemias within 3-6 mo. RadLV-induced lymphomas can elicit cytotoxic responses in vitro in lymphocytes of preimmunized syngeneic mice, a reaction that is dependent on the expression of membrane-associated viral antigenicity. As soon as 5 d after RadLV inoculation, and during the entire leukemogenic process, suppressor T cells are detectable in the spleen that are capable of specifically abrogating generation of syngeneic anti-tumor cytotoxic cells in vitro. Mice exposed to fractionated x irradiation do not develop suppressor cells and their splenocytes may be stimulated in vitro to generate cytotoxicity toward RadLV-induced leukemias. These findings suggest that although RadLV has been isolated from radiation-induced leukemias, x-ray- and RadLV-induced leukemogenesis do not seem to involve a common viral etiology, and that induction of suppressor cells during RadLV leukemogenesis may be essential for tumor progression.

Immunization of mice with heavily irradiated syngeneic Moloney lymphoma cells evokes antibodies against the major viral envelope antigen, gp71, and the Moloney virus-induced cell surface antigen (MCSA). A9HT cells, an L-cell subline, react with the antibodies against the viral envelope antigen only; this reaction can be completely inhibited by virus or purified gp71. Reactivity to Moloney lymphoma cells (YAC) was only partially inhibited (maximum 30%) or not at all. This can be attributed to the reaction of the YAC cells with antibodies directed against MCSA, a nonvirion cell surface component according to both biological and biochemical evidence. Antibody-induced capping of gp71 or p15(E) did not change the membrane distribution of MCSA or H-2, indicating that these antigens represent distinct entities on the cell surface. MCSA showed only minimal capping and thereby differed in behavior from both H-2 and virion antigens. gp71 could be capped by the mouse antiserum as revealed by subsequent staining with monospecific anti-gp71 antiserum. Under ordinary test conditions this reactivity is overshadowed by the reaction against MCSA. The lack of MCSA capping reflects a difference in anchorage of this antigen.