Recently, a streptococcal preparation, OK-432 has been used successfully as an immunopotentiator for immunotherapy in patients with malignant tumors in Japan. In this paper, we report that the administration of OK-432 augments the cytotoxic activity of peripheral blood lymphoid cells against a natural killer (NK) cell-sensitive erythroleukemic cell line, K562, in tumor patients. In patients before or after surgery, sufficient amounts of OK-432 strongly augmented the cytotoxic activity within 3 days after the initial administration of OK-432. Thereafter the levels of cytotoxicity declined rapidly. The administration of a lower dose of OK-432 gave a lower increase in cytotoxicity. Enhanced cytotoxicity occurred with the reintroduction of OK-432 but remained at lower levels of activity. Characterization and fractionation of OK-432-induced effector cells revealed that the augmented cytotoxicity seemed to be carried mainly by NK cells. A low titer of interferon was detected in 3 of 10 patients within 72 hr after the first inoculation of the agent. Furthermore, we discuss the potency of OK-432 for the induction of interferon in detail.

Adjuvants, Immunologic↗

PubMed1981

Adult onset mucocutaneous lymph node syndrome with coronary aneurysm.

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Adolescent↗

PubMed1981

Cytotoxicity of cultured mouse spleen cells against natural killer-sensitive target cells. Characterization of the effector cells.

Killer cells with natural killer (NK) cell-like target selectivity were generated when C3H or C57BL/6 mouse spleen cells were cultured in vitro. Compared with NK cells, the in vitro-generated killer cells with NK-like reactivity were slightly adherent to nylon wool fibers, a little more sensitive to anti-Thyl.2 antibody plus complement and almost entirely resistant to cytotoxic treatment with anti-asialo GM1 antiserum which is selectively cytotoxic to NK cells. The culture of NK-depleted spleen cells yielded a lower degree of NK-like cytotoxicity, thus it seems likely that NK cells changed to NK-like killer cells in vitro. Competitive inhibition studies suggested that the in vitro-generated NK-like cells were different from alloantigen-reactive killer T cells. The above results, therefore, might suggest that in vitro-induced NK-like cells do not belong to any known subset of killer cells.

Animals↗

PubMed1981

[Natural killer cell activity test].

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Chromium Radioisotopes↗

PubMed1980

Stimulation of human lymphocyte subpopulations by protein A from Staphylococcus aureus.

Protein A from Staphylococcus aureus is known to stimulate human lymphocytes. Using 3H-thymidine incorporation, virus plaque assay and induction of cytotoxic T lymphocytes (CTL), this study showed that soluble or insoluble protein A stimulated different lymphocyte subpopulations. Soluble protein A is highly mitogenic to T lymphocytes. In both 3H-thymidine incorporation and virus plaque assay, its maximum stimulation was as high as the stimulation by the nonspecific mitogens phytohemagglutinin and concanavalin A, and a higher CTL response than that induced by phytohemagglutinin or concanavalin A was induced. Mitogenic activity to B lymphocytes was negligible. S. aureus (Cowan I strain) is itself considered to be an insoluble form of protein A and is 3--4 times more mitogenic to B lymphocytes than pokeweed mitogen without any increase in virus plaque-forming cells. No mitogenicity was noted to T lymphocytes. Sepharose CL-4B-protein A, also known as insoluble protein A, stimulated both T and B lymphocytes effectively, but its mitogenicity to T lymphocytes was considered to be due to the soluble protein A released from the Sepharose CL-4B beads.

B-Lymphocytes↗

PubMed1980

Activation of secondary cytotoxic lymphocytes by cell-free factors from I-region-primed and D-region-primed lymphocytes.

Cell co-operation in the generation of secondary cytotoxic responses was studied by selectively sensitizing lymphocytes in mixed lymphocyte culture (MLC) across I or D region difference and by combining the primed lymphocytes in the secondary MLC. Secondary cytotoxic responses were induced in D-region-primed lymphocytes by restimulation with the original priming D-region antigens, by co-culturing with the I-region-primed lymphocytes in the presence of the priming I-region antigens, or by cell-free supernatants obtained 24 h after the restimulation of D-region-primed lymphocytes and I-region-primed lymphocytes, The active MLC supernatants produced by both I-region-primed and D-region-primed cells also induced accelerated proliferative responses in D-region-primed lymphocytes. Heat-treatment or ultraviolet irradiation of the stimulator cells eliminated the capacity of the cells to induce the production of CTL-helper factor in I-region-primed and D-region-primed lymphocytes. It was concluded that both I-region-primed and D-region-primed lymphocytes produce a cell-free factor which induces proliferation and secondary cytotoxicity in D-region-primed lymphocytes. The possible participation of D-region reactive helper T cells and D-region reactive cytotoxic T cells in the cytotoxic responses to D-region antigens in the absence of I-region difference is discussed.

Animals↗

PubMed1980

Generation of autoreactive cytotoxic lymphocytes by spontaneously established autologous lymphoblastoid cell line.

Using spontaneously established autologous and allogeneic LCL as stimulator and target cells, we studied the generation of autoreactive cytotoxic T lymphocytes (CTL) in primary and secondary autologous MLC. In the primary autologous MLC, cytotoxic activity was detected on the 6th day and was found to be specific to autologous LCL. In the secondary autologous MLC, cytotoxic activity was detected earlier on the 3rd day, and was at a higher level than in the case of the primary autologous MLC. This cytotoxic activity was induced in both the primary and the secondary autologous MLC when T lymphocytes were used as responder cells. When autologous LCL-primed lymphocytes were used as responder cells in the secondary MLC, autologous LCL-specific CTL were not only generated by autologous LCL but also by allogeneic LCL, and the autologous LCL-specific CTL induced by allogeneic LCL was thought to be due to the nonspecific helper effect of allogeneic LCL-stimulation.

Animals↗

PubMed1980

Augmentation of mouse natural killer cell activity by a streptococcal preparation, OK-432.

Streptococcal immunopotentiator OK-432 (NSC-B116209) augmented the natural killer (NK) cell activity of peritoneal exudate cells (PEC) in inbred C57BL/6 mice given ip injections of 0.1 mg OK-432 per mouse. The cytotoxic activity of PEC increased as early as 1 day after inoculation, reached its peak on day 3, and gradually declined thereafter, YAC-1, K562, and MOLT-4 target cells were more sensitive to PEC than were EL 4 and P815 target cells. The elimination of adherent cells by a nylon wool column enriched the proportion of cytotoxic cells among PEC. Nylon wool column-passed PEC were resistant to treatment with anti-Thy 1.2 antibody plus complement and sensitive to anti-asialo GM1 serum plus complement. Because 1:40-diluted rabbit antiserum against glycosphingolipid asialo GM1 is capable of eliminating mouse NK cell activity and is not cytotoxic to killer T-cells, the above results strongly suggest that OK-432 augments the NK cell activity in mice.

Animals↗

PubMed1980

Effects of corticosteroids on natural killer cell activity in systemic lupus erythematosus.

The effects of corticosteroids on the natural killer (NK) cell activity of human peripheral blood lymphocytes were evaluated. When six untreated female patients with systemic lupus erythematosus were compared with fifteen age-matched, corticosteroid-treated female patients, NK activity in the latter was significantly suppressed. Although the administration of high doses seemed to suppress cytotoxicity to a greater extent, there was no close correlation between the daily doses of steroids and NK activity. When cytotoxicity levels were followed before and during corticosteroid therapy in the same patient, NK activity decreased markedly during treatment, particularly in patients on high-dose corticosteroids.

Adult↗

PubMed1979

Natural killer cell activity in systemic lupus erythematosus.

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Adolescent↗

PubMedDate not supplied

Myeloblastoma formation in acute myeloid leukemia.

The cell surface markers on the leukemic cells of 76 patients with adult acute myeloid leukemia (AML) have been analyzed by indirect immunofluorescence, and the presence of CD56+ leukemic cells was detected in ten of these patients. Four of these 10 CD56+ AML patients developed extramedullary myeloblastomas and in two of them an intracranial myeloblastoma. In contrast, in the remaining 66 CD56- AML patients, only one patient developed a myeloblastoma formation of the subcutaneous. It may be that the CD56 antigen which is an isoform of the neural cell adhesion molecule (NCAM), expressed on neurons, satellite cells of skeletal muscle cells, and on stromal cells, binds these tissues by a homophilic mechanism. CD56+ leukemic cells are capable of invading and of surviving in extramedullary tissues, where they proliferate and develop into a myeloblastoma. Because of this possibility, CD56+ AML patients should be carefully monitored for signs of myeloblastoma formation.

Adolescent↗

PubMedDate not supplied

Multiple myeloma with coexistent myelofibrosis: improvement of myelofibrosis following recovery from multiple myeloma after treatment with melphalan and prednisolone.

We describe a case of multiple myeloma associated with myelofibrosis. This patient had hepatosplenomegaly, moderate anemia with anisocytosis and nucleated red blood cells, and Bence-Jones protein (kappa) in the urine. A bone marrow biopsy showed extensive marrow fibrosis and proliferation of numerous immature plasma cells containing kappa light chain in the cytoplasm. Melphalan-prednisolone therapy not only facilitated the disappearance of the immature plasma cells but also resulted in an improvement of myelofibrosis in the bone marrow. The immature plasma cell proliferation and marrow fibrosis in the bone marrow were seen again after interruption of chemotherapy. Therefore, this myelofibrosis may be secondary to the coexistent multiple myeloma.

Agammaglobulinemia↗

PubMedDate not supplied

Hemophagocytosis in autoimmune disease.

Reactive hemophagocytic syndrome (HPS) is known to be associated with various autoimmune diseases, as well as infection and/or malignancy. Here we review the features of autoimmune-associated HPS and describe the possible role of autoantibodies, especially antiphospholipid antibodies (aPL), in HPS based on data obtained from our own patients.

Antibodies, Antiphospholipid↗