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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nonspecific suppressor cells were induced during in vitro culture of normal mouse spleen cells (SPC) using the Marbrook culture system. The suppressor cells inhibited both the primary and secondary antibody-formation responses antigen nonspecifically in vitro, and both IgM- and IgG-responses were inhibited. The supernatants from suppressive precultured cells were not suppressive. The suppressor cells also inhibited the response of allogeneic SPC beyond H-2 compatibility. The induction of the suppressor cells did not require the presence of antigen but required fetal calf serum (FCS) or both FCS and 2-mercaptoethanol (2-ME). The suppressor cells were generated from the nylon-wool adherent, radiation-sensitive T cell population. On the other hand, the suppressor cells were nylon-wool nonadherent, relatively radiation-sensitive T cells. Actively antibody-producing cells were not affected by the suppressor cells. The suppressor cells inhibited the mitogenic responses of normal SPC to phytohemagglutinin-P (PHA), bacterial lipopolysaccharide (LPS) and concanavalin A (Con A). The suppressor cells themselves inhibited the growth of EL4 cells (T-cell leukemia of C57BL/6 mouse origin) and MOPCll cells (B cells, plasmacytoma of BALB/c mouse origin) even at a low effector-to target cell ratio (E:T ratio = 1:1), but did not kill these tumor cells. These results indicate that the target cells of the suppressor cells are both T and B cells, and that the mechanism of action of the suppression is either inhibition of proliferation or inhibition of early events in the course of the immune response.
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PMID:Spontaneously induced suppressor cells in vitro: nonspecific suppression of in vitro antibody formation. 646 Jan 59

Conjugates of the monoclonal antibody anti-Thy 1:1 (OX7) and ricin have been constructed, using a thioether bond, such that the ricin no longer can bind Sepharose or asialofetuin. These conjugates were found to be very toxic to Thy 1:1 expressing AKR-A cells whereas they showed little toxicity to Thy 1:2 expressing EL4 cells. By comparison, OX7-ricin conjugates which retained galactose-binding capability were still highly toxic to EL4 cells and this toxicity was antagonized by lactose. A second conjugate made from the W3/25 monoclonal antibody was constructed. The W3/25-ricin conjugate which had lost Sepharose-binding capacity was toxic to W3/25 antigen-expressing rat T-leukaemia cells. This is in sharp contrast to the disulphide linked W3/25-ricin A-chain conjugate which is totally inactive, suggesting that the role of the B-chain in membrane transport of the A-chain into the cytosol is independent of galactose recognition.
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PMID:Antibody-ricin conjugates: a method of linkage which blocks the galactose binding site of ricin. 647 50

Mouse thymocytes and spleen cells from unprimed C57BL/6 donors generate broadly reactive cytotoxic cells during 5 days of culture in vitro with polyinosinic acid (5') (poly(I] and/or supernatant from PMA-treated EL4 leukemia cells which contains interleukin 2 (IL-2) activity. We refer here to such cytotoxic cells as "supplement-induced cytotoxic cells" or SICC. Thymocytes are dependent on the supernatant factor(s), whereas spleen cells are usually stimulated by poly(I) alone. Polyinosinic acid acts synergistically with supernatant factor(s) to stimulate generation of SICC by both thymocytes (SICC-T) and spleen cells (SICC-S) when the IL-2 activity of the supernatant is inadequate alone. SICC can be generated by both splenocytes and thymocytes in medium supplemented with fetal calf serum or syngeneic plasma. SICC are active in 4 hr 51Cr-release tests against syngeneic, allogeneic, and xenogeneic tumors but not against lipopolysaccharide-induced lymphoblasts. Embryonic fibroblasts, too, are sensitive to SICC generated by thymocytes. In complement-dependent depletion tests, cytotoxic activity is partially sensitive (SICC-T) or fully sensitive (SICC-S) to anti-Thy-1 and -H-2 but not to anti-Lyt-1, -Lyt-2, or -asialo GM1.
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PMID:Supplement-induced cytotoxic cells (SICC) generated from mouse thymus or spleen cells cultured in the presence of interleukin 2 and/or polyinosinic acid. 660 5

A method is described for preparing specific cytotoxic agents by linking intact ricin to antibodies in a manner that produces obstruction of the galactose-binding sites on the B chain of the toxin and so diminishes the capacity of the conjugate to bind non-specifically to cells. The conjugates were synthesised by reacting iodoacetylated ricin with thiolated immunoglobulin and the components of conjugate with reduced galactose-binding capacity were separated by affinity chromatography on Sepharose (a beta-galactosyl matrix) and asialofetuin-Sepharose. Fluorescence-activated cell sorter (FACS) analyses revealed that the fraction of a monoclonal anti-Thy1.1-ricin conjugate that passed through a Sepharose column had markedly diminished capacity to bind non-specifically to Thy1.2-expressing CBA thymocytes and EL4 lymphoma cells. The fraction of conjugate that passed through an asialofetuin-Sepharose column displayed no detectable non-specific binding. Both fractions of conjugate were potent cytotoxic agents for Thy1.1-expressing AKR-A lymphoma cells in tissue culture. They reduced the [3H]leucine incorporation of the cells by 50% at a concentration of 2-5 pM. Comparable inhibition of EL4 cells was only achieved with 3000-7500-fold greater concentrations of conjugate. By contrast, the fraction of anti-Thy1.1-ricin that retained Sepharose-binding capacity showed marked non-specific binding and toxicity to EL4 cells. A conjugate with diminished galactose-binding capacity was also prepared from the W3/25 monoclonal antibody which recognises an antigen upon helper T-lymphocytes in the rat. It elicited powerful and specific toxic effects upon W3/25 antigen-expressing rat T-leukaemia cells. This finding is of particular importance because isolated ricin A-chain disulphide-linked to W3/25 antibody is not cytotoxic. The property of the B-chain in intact ricin conjugates that facilitates delivery of the A-chain to the cytosol thus appears to be independent of galactose recognition. It is concluded that the 'blocked' ricin conjugates combine the advantages of high potency, which is often lacking in antibody-A-chain conjugates, with high specificity, which previously was lacking in intact ricin conjugates.
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PMID:Blockade of the galactose-binding sites of ricin by its linkage to antibody. Specific cytotoxic effects of the conjugates. 660 47

The adoptive transfer of resistance to tumor grafts with cloned interleukin 2 (IL-2)-dependent cytotoxic T-cell lines was examined. Two clones were used: clone CTLL-A2 which recognizes H-2Dd determinants and clone CTLL-R5 which recognizes a unique cell surface antigen of BALB/c leukemia RL male 1. Systemic transfer of resistance with these clones was accomplished only when exogenous (rat or human) IL-2 was administered at the same time. Intraperitoneal injection of CTLL-A2 cells accelerated rejection of sarcoma Meth A (H-2Dd), but not ascites sarcoma BP8 (H-2k) or leukemia EL4 (H-2b) inoculated subcutaneously into C57BL/6 mice. CTLL-R5 cells were examined in local (Winn tests) as well as systemic transfer experiments. When mixed with leukemia cells before subcutaneous injection, they suppressed the growth of leukemia RL male 1 without exogenous IL-2. When injected intraperitoneally, CTLL-R5 cells inhibited the growth of subcutaneous grafts of leukemia RL male 1 only when exogenous IL-2 was administered at the same time. CTLL-R5 did not inhibit the growth of other radiation-induced BALB/c leukemias.
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PMID:Characterization of interleukin 2 (IL-2)-dependent cytotoxic T-cell clones. V. Transfer of resistance to allografts and tumor grafts requires exogenous IL-2. 661 Apr 78

Monocytes derived from peripheral blood of patients with rheumatoid arthritis (RA) had a marked defect in their bactericidal activity against Staphylococcus albus and Listeria monocytogenes; whereas the phagocytic capacity of monocytes from RA patients for both Staph. albus and Shigella flexneri was similar to that of monocytes from healthy subjects. There were no significant differences between the patient and control groups with regard to antibody dependent cellular cytotoxicity (ADCC) of monocyte against antibody-coated EL4 leukemia tumor cells. No correlation was observed between the rheumatoid factor (RF) titer in the serum of RA patients and the ADCC capacity of their monocytes. The ADCC of normal monocytes was reduced markedly following their incubation with serum from RA patients. It suggested that the defect in bactericidal activity in monocytes from RA patients may explain, at least in part, the susceptibility of RA patients to infections.
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PMID:Monocyte function in rheumatoid arthritis. 676 49

The objective of the present study was to establish a model system for the evaluation of passive immunotherapy of murine leukemias. Monoclonal antibodies directed at T lymphocyte differentiation antigens (Thy 1 and Lyt 2) were tested for their effect on tumors that were grown in hosts congenic for the target antigen. Tumor challenges were selected that were at least 500 times the dose that was lethal in 50% of untreated controls. The A strain leukemia, ASL.1, was transplanted subcutaneously into a/Thy 1.1 congenic hosts. Intraperitoneal administration of anti-Thy 1.2 monoclonal antibodies of the IgG3 and IgM classes reduced tumor growth. Up to 90% of the mice receiving antibody of the IgG3 subclass failed to develop tumors, whereas IgM antibodies prolonged survival time, but the mice eventually died of tumors. Antibody was most effective if administered within 24 hr of tumor inoculation; delay of antibody injection for 48 hr prolonged host survival but did not eradicate cells at the injection site or prevent metastases. The C57BL/6-derived tumors, ERLD and EL4, were evaluated for susceptibility to treatment with antibody directed at the Lyt 2.2 alloantigen using the protocol that was effective in treating aSL.1. Monoclonal antibody of the IgG2a subclass was effective in the case of C57BL/6/Lyt 2.1 congenic mice bearing ERLD, but caused a decrease in survival time of mice bearing the transplanted EL4 tumor. Thus, antibody of the appropriate immunoglobulin subclass can be effective in controlling tumor growth if administered in the optimal treatment regimen, but inherent features of the tumor cell ultimately determine whether abrogation or enhancement of growth will occur.
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PMID:Immunotherapy of murine leukemias by monoclonal antibody. I. Effect of passively administered antibody on growth of transplanted tumor cells. 678 49

Changes in sialoglycoconjugates and glycosphingolipid (GSL)5 metabolism were demonstrated in mouse EL4, P52 and YAC-1 lymphoma and L1210 leukemia cell lines treated with beta-interferon (IFN). Expression of cell surface (neuraminidase-releasable) sialic acid on IFN-treated cells was markedly elevated (three- to six-fold). The increase in neuraminidase-releasable sialic acid is contributed by sialoglycoproteins and particularly by cell-surface gangliosides in IFN-treated cells. Incorporation of [3H]-galactose into all GSL was elevated in IFN-treated cells. Thin-layer chromatographic analysis of GSL of IFN-treated cells showed an increase in several GSL homologues with striking changes in ganglioside with chromatographic migration of GM2, GM1, and GD1a relative to control cells. IFN-treated tumor-cell lines became resistant to lysis by virus-induced IFN-activated natural killer (NK) cells, as shown previously, but addition of neuraminidase to IFN-treated and untreated cells caused only a moderate increase in NK-sensitivity. This suggests that IFN-mediated protection of target cells from NK lysis was not due to a preferential masking of target structure by elevated levels of sialic acid. These membrane-associated changes in GSL and sialic acid in IFN-treated cells may be potentially significant, because a correlation between certain GSL expression, sialic acid phenotype and susceptibility of target cells to NK-cell-mediated lysis have been found in several other systems.
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PMID:Interferon-induced increase in neuraminidase-releasable sialic acid and glycosphingolipid metabolism in mouse lymphoma and L1210 leukemic cell lines: correlation with susceptibility to natural killer cell-mediated lysis. 683 56

Cytotoxic hybridomas were generated by polyethylene glycol-induced fusion of cytotoxic T lymphocytes (CTL) and BW5147 lymphoma cells. The CTL populations used for fusion were obtained from BALB/c (H-2d) mice primed with leukemia EL4 of C57BL/6 (H-2b) and restimulated either in vivo or in vitro. To circumvent possible CTL-mediated nonspecific lysis of BW5147 cells during fusion, the CTL were transiently inactivated by trypsin prior to fusion. Four cytolytically active hybridomas were obtained, cloned, and subcloned. Hybrid clones lysed all H-2b leukemic target cells tested but not lipopolysaccharide- or concavanalin A-stimulated C57BL/6 lymphoblasts or non-H2b target tumor cells. The mechanism of hybridoma-mediated killing of target cells in vitro appears to be similar to that of parental CTL, although some differences have been observed. The hybridomas appear to possess neither natural killing nor antibody-dependent cytolytic activity. Clones of hybrids propagated in culture for over 6 months without the addition of known external stimulus (i.e., independent of cell growth factor and antigen) exhibit specific lytic activity against H-2b tumor cells. Such autonomous hybridomas will provide a tool for studying the mechanism of CTL-mediated lysis and the nature of the CTL receptors.
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PMID:Cytotoxic T lymphocyte hybridomas that mediate specific tumor-cell lysis in vitro. 697 38

A limiting dilution mixed leukocyte-tumor cell microculture system was used to quantitate cytolytic T lymphocytes and their precursors (CTL-P), which infiltrate tumors induced by injection of Moloney sarcoma-leukemia virus (MSV-MoLV) complex into C57BL/6 mice. Leukocyte populations obtained from tumors collected on day 10 after virus injection were found to contain significantly higher frequencies of operationally defined (tumor-specific) CTL-P than either peripheral blood leukocytes (PBL) or spleen cells from the same animals. When these frequencies were normalized according to the content of Lyt-2+ T cells in each tissue, average CTL-P frequencies were found to be 1/9 in tumor-infiltrating cells vs. 1/41 in PBL. These results directly demonstrate selective accumulation of CTL-P in the tumor mass. A number of clonal isolates obtained from tumor-infiltrating leukocyte populations were expanded and studied for cytolytic activity and specificity. Of 11 isolates, 10 were found to have high cytolytic activity, leading to 50% lysis of the syngeneic MoLV-derived tumor target cells in 3.5 h at lymphocyte:target cell ratios ranging from 0.5:1 to 3.2:1. Furthermore, five randomly selected clones showed H-2 restriction by their selective lytic activity against MoLV-derived syngeneic MBL-2 target cells and their lack of activity against either MoLV-derived allogeneic (LSTRA) tumor cells or against syngeneic (EL4) or allogeneic (P815) target cells unrelated to MoLV.
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PMID:Quantitation and clonal isolation of cytolytic T lymphocyte precursors selectively infiltrating murine sarcoma virus-induced tumors. 697 2


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