Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.148 (Thy1)
 1,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Specific antitumor effects of lymphokine activated lymphocytes obtained from tumor-bearing mice after intratumoral injection of IL-2 were studied. Furthermore, effects of preoperative endoscopic intratumoral injection combined IL-2 and Lentinan or OK-432 were clinically studied against gastric cancer. The results were as follows: After intratumoral consecutive injection of recombinant human IL-2 (rhIL-2), the splenocytes of these mice were cultured with rhIL-2 and the effector cells were obtained. 1) Adoptive transfer of the effector cells specifically diminished the size of the host tumor and prolonged the life span of the mice. 2) The analysis of the surface antigens indicated the Thy1.2, Thy1.2+ L3T4+ cells increased in the effector cells as the specific cytotoxicity of them were augmented. 3) Preoperative endoscopic intratumoral injection combined IL-2 and Lentinan or OK-432 induced immunocytes including antigen-presenting cells in the site of the gastric cancer, and increased the IL-2R and the LAK activity of PBL. This method was considered as effective as an adjuvant treatment of gastric cancer surgery as a in vivo sensitization.
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PMID:[Intratumoral injection of biological response modifier (BRM)]. 194 92

In our companion paper we have reported that cell-mediated immunity of mice bearing renal cell carcinoma is profoundly suppressed. The non-responsiveness of such animals was found to be attributable to Renca cells themselves and to splenic lymphoid cells that down-regulate other fully capable lymphoid cells. In this communication the lymphoid cell source of suppression within Renca-bearing mice has been explored with the aim of identifying phenotypes of the responsible cells, the manner by which suppression is mediated, and initial ways by which suppression may be eliminated. A plastic-adherent cell bearing the Thy1.2 surface marker as well as the Lyt1 and Lyt2 antigens has been found to operate, perhaps in conjunction with macrophages, to down-regulate lymphokine-activated killer (LAK) cell development for natural killer (NK) and non-NK targets that include Renca cells themselves. The splenic suppressor cells lost the capacity to suppress the NK response of normal recipient mice upon shallow irradiation (250 rad) prior to adoptive transfer. Spleen cells, presumably macrophages, from Renca-bearing mice were found to suppress the generation of LAK and NK cells in vitro by synthesizing prostaglandins. Indomethacin, a prostaglandin synthetase inhibitor, blocked the induction of suppression both in vitro and in vivo, suggesting the presence of endogenous prostaglandins in Renca-bearing mice. The suppression seen in Renca-bearing mice that derives from multiple sources and has been prevented by two separate methods has been discussed from the viewpoint of the inter-relatedness of the sources.
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PMID:Immunosuppression in murine renal cell carcinoma. II. Identification of responsible lymphoid cell phenotypes and examination of elimination of suppression. 197 26

We investigated the effect of beta-cyclodextrin-benzaldehyde (CDBA) on lymphokine-activated killer (LAK) cell activity of spleen cells from normal or RCT(+)H-2(+)-sarcoma-bearing C3H/He mice. CDBA augmented the induction of LAK cytotoxicity in vitro against RCT(+)H-2+ tumor cells by IL-2, whereas the culture with CDBA alone did not. In a LAK cytotoxicity assay in vitro, the augmentative effect of CDBA was strongly exerted against spleen cells originating from 2-week-tumor-bearing mice, rather than those from normal mice or mice that had born tumors for 5 weeks. Such an augmentative effect was not observed against other tumor cells (YAC-1, D-6, Colon-26 and EL-4 cells) non-specifically. When the intravenous adoptive transfer of LAK cells was carried out in the mice, LAK cells from tumor-bearing mice induced by combined culture with interleukin-2 (IL-2) and CDBA markedly inhibited the pulmonary metastases of RCT(+)H-2+ tumor, while neither LAK cells from the same tumor-bearing mice induced by only IL-2 nor those from normal mice inhibited the pulmonary metastasis. The majority of LAK cells induced either by IL-2 plus CDBA or by IL-2 alone were found to be Thy1.2+ and asialoGM1+ cells by flow-cytometric analysis, but no obvious phenotypical difference was observed between them. However, the most significant effect of CDBA might be the maintenance of the Lyt-2+ cell level in the spleen cells from tumor-bearing mice. These results suggested that the costimulation of spleen cells with IL-2 and CDBA might induce cytotoxic T cells specific for syngeneic tumor cells.
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PMID:Augmentation of murine lymphokine-activated killer cell cytotoxicity by beta-cyclodextrin-benzaldehyde. 200 9

Specific antitumor effects of lymphokine-activated lymphocytes obtained from tumor-bearing mice after intratumoral injection of IL-2 were studied. Inbred C57BL/6 mice bearing syngeneic tumor (B16,3LL) were used. After intratumoral consecutive injection of recombinant human IL-2 (rhIL-2), the splenocytes of these mice were cultured with rhIL-2 and the effector cells were obtained. Specific antitumor effects of the effector cells against B16 and 3LL were studied in vitro and in vivo. Surface antigens of them were also analysed. The results were as follows: 1) 51Cr-release test under coculture with rhIL-2 showed that cytotoxicity against the host tumor cells with the effector cells became specifically augmented. 2) Winn assay showed specific inhibition of the host tumor growth with the effector cells. 3) Adoptive transfer of te effector cells specifically diminished the size of the host tumor and prolonged the life span of the mice. 4) The lymphokine-activated lymphocytes obtained from normal and non-treated tumor-bearing mice had no specific antitumor effect. 5) The analysis of the surface antigens indicated that Thy1.2+L3T4+ T cells increased in the effector cells as the specific cytotoxicity of them were augmented, while in the effector cells from normal and non-treated tumor-bearing mice, Thy1.2+L3T4+ T cells decreased and Thy1.2+Lyt2+ T cells increased.
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PMID:[Specific antitumor effect of lymphokine-activated lymphocytes obtained from tumor-bearing mice after intratumoral injection of interleukin-2 (IL-2)]. 205 76

The immunogenicity and immunosensitivity of primary mouse cell lines transformed by bovine papilloma virus 1 (BPV1) DNA were studied in a syngeneic mouse model by determining cell-mediated cytotoxicity in the spleens of mice immunized with the transformed cells. One of the cell lines induced the generation of cell-line-specific Thy1.2-positive cytotoxic effector cells. However, most of the cell lines tested induced the generation of Thy1.2-positive effector cells, which in addition to BPV1-transformed cells were able to lyse a syngeneic cell line transformed by methylcholanthrene. The lysis of BPV1- and methylcholanthrene-transformed cell lines was mediated by recognition of the same antigenic determinants expressed on these cells, and all the BPV1-transformed cell lines were sensitive to lysis by these nonspecific effector cells of the lymphokine-activated killer (LAK) type.
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PMID:Generation of cell-mediated cytotoxicity against bovine-papilloma-virus-transformed primary mouse cell lines. 215 31

More than 80% of BALB/c mice bearing BAMC-1 ascites tumor were completely cured after five consecutive (once every 2 days) i.p. injections of a 0.1 mg dose of OK-432, beginning on day 2 after tumor implantation. The antitumor effect of OK-432 was abolished in athymic nu/nu mice and in anti-thymocyte globulin-treated euthymic BALB/c mice, so although OK-432 treatment did increase the length of survival, all animals eventually died as a result of tumor growth. When peritoneal exudate cells (PEC), obtained on day 12 from OK-432-treated BAMC-1-bearing euthymic mice were evaluated for in vivo tumor neutralization activity, all mice receiving an i.p. injection of the admixture of the nonadherent PEC (1 X 10(7) cells) with BAMC-1 cells (1 X 10(5)) survived for more than 60 days. When the same nonadherent PEC (1 X 10(7) cells) were i.p. transferred adoptively 1 day after the inoculation of 1 X 10(5) BAMC-1 tumor cells, again all mice survived. When these in vivo active PEC were tested for cytotoxicity in vitro against fresh BAMC-1 tumor cells, natural killer (NK) sensitive syngeneic RL male 1, NK-sensitive allogeneic YAC-1 cells, NK-resistant syngeneic Meth-A cells, allogeneic tumor cells (EL4, B16, and P815) and xenogenic human cells, the PEC were found to be capable of lysing BAMC-1 tumor cells together with almost all of the other tumor cells, including NK-resistant cells. Nonadherent PEC contained at least two subpopulations of killer cells. One, directed to syngeneic BAMC-1 cells, was both Thy1.2 and asialo GM1 positive, and another, directed to allogeneic YAC-1 cells, was asialo GM1 positive but Thy1.2 negative. A cold target inhibition assay also suggested the presence of more than two subpopulations. These results indicate that T cells play a determined role in the immunotherapeutic effect of OK-432 on BALB/c mice bearing BAMC-1 tumor, although the participation of activated macrophages could not be excluded. The cells responsible for killing BAMC-1 and other tumor cells appearing in the PEC on day 12 were characterized as containing at least two kinds of lymphokine-activated killer cells.
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PMID:Pronounced antitumor effect of LAK-like cells induced in the peritoneal cavity of mice after intraperitoneal injection of OK-432, a killed streptococcal preparation. 242 68

Interleukin-2 (IL-2) augments natural killer (NK) activity as well as generating effector cells named lymphokine activated killer cells (LAK) which are capable of lysing a wide spectrum of target cells. A large body of evidence has been accumulated to evaluate the relationship between NK and LAK cells and conflicting results have been reported. Our study was addressed to further analyse this relationship and in particular to investigate whether in a short incubation IL-2 is merely capable of augmenting the activity of pre-existing killer cells, or whether it can also promote the differentiation of precursor cells. Eighteen-hour culture of mouse spleen cells in human recombinant IL-2 induced a DNA-synthesis-independent generation of cytotoxic cells bearing an NK phenotype (aGM-1+, Thy1.2+/-, CD8-, CD4-). These were generated from precursor cells also bearing an NK phenotype, recovered either from low density Percoll fractions enriched in lytic cells with LGL morphology as well as from high density fractions devoid of LGL and cytotoxic activity.
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PMID:Overnight incubation of mouse spleen cells in recombinant IL-2 generates cytotoxic cells with NK characteristics from precursors enriched with or devoid of LGL. 249 99

Tumor-infiltrating lymphocytes (TILs) have potent antitumor effects in murine models of advanced disease. Although these cells are 50-100 times more potent than lymphokine-activated killer cells against micrometastases, their antitumor benefits are virtually nonexistent against large tumor burdens unless cyclophosphamide is added to the immunotherapy regimen. In an effort to determine the effects of cyclophosphamide on TILs obtained from tumor-bearing animals, we harvested tumors from animals having received either 0, 50, or 100 mg/kg cyclophosphamide intravenously and investigated the expansion, cytotoxicity, and phenotypic expression of these TILs co-cultured in vitro with recombinant interleukin-2. TILs obtained from animals given cyclophosphamide, demonstrated a greater fold expansion than TILs obtained from normal animals (mean fold expansion on day 59 of culture: 85, 400, and 150 for TILs obtained from animals given 0, 50, and 100 mg/kg cyclophosphamide, n = 3 consecutive experiments). In addition, these TILs demonstrated enhanced cytotoxicity compared to controls [effector to target ratio 4:1, day 16 TILs, % lysis: 24, 35, and 45%, cyclophosphamide 0, 50, and 100 mg/kg, respectively, against the MCA-102 sarcoma, natural killer (NK) insensitive tumor; 29, 38, and 56% against the YAC-1 lymphoma, NK sensitive tumor]. Similar results were seen with day 34 and day 59 TILs. When phenotypic analysis was performed, TILs obtained from animals given cyclophosphamide consistently demonstrated a greater percent expression of the Thy1.2 and Lyt-2 antigens up to day 59 of culture when the experiments were terminated. The NK cell marker 49H.8 was expressed on the majority of TILs and its expression did not change with respect to the cyclophosphamide concentration. The increase in TIL number and cytotoxicity seen with cyclophosphamide given intravenously before tumor harvest could have important ramifications for human immunotherapy with TILs.
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PMID:Tumor-infiltrating lymphocytes cultured in recombinant interleukin-2: enhancement of growth, cytotoxicity, and phenotypic expression of cytotoxic T-cell antigens by cyclophosphamide given intravenously prior to tumor harvest. 278 92

Murine cytomegalovirus (MCMV)-immune lymph node (LN) cells were generated following 4 days culture of draining popliteal LN cells removed after bilateral hind footpad inoculation of mice with 4 X 10(2) p.f.u. MCMV. This cell population expressed both cytotoxic activity against MCMV-infected mouse embryo fibroblasts (MEF) and the capacity to release lymphokine upon stimulation with MCMV-infected MEF. Cytotoxicity and lymphokine release were Class I, H-2-restricted, virus-specific and dependent upon Thy1. 2+, Lyt2+ cells. Mixing of 5 X 10(5) MCMV-immune T cells with an excess of syngeneic MCMV-infected MEF stimulators produced detectable levels of the lymphokine interleukin-3 by 1 h, with a maximum rate of its release between 1 and 6 h and plateau levels by 14 h. The capacity to stimulate virus-specific MCMV-immune T cells was acquired by MEF at 1 h after MCMV infection with maximum stimulator ability attained by 8 h. In the presence of a fixed number of MCMV-immune T cells, and titration to excess of syngeneic 3 h or 18 h MCMV-infected MEF, lower interleukin-3 plateau levels were obtained with 3 h than with 18 h MCMV-infected stimulators. This suggested that fewer T cells responded to 3 h than to 18 h MCMV-infected MEF.
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PMID:The cytotoxic response to murine cytomegalovirus. III. Lymphokine release and cytotoxicity are dependent upon phenotypically similar immune cell populations. 286 28

Activated killer (AK) cells were generated in spleen-cell cultures derived from tumor-bearing hosts (TS) whereas, under the same conditions, cultured normal spleen cells (NS) gave little cytotoxicity. The AK effectors were primarily Thy1+, AGM1- and Lyt2- and thus were neither classic cytotoxic T lymphocytes (CTL) nor classic NK cells. These AK cells selectively killed tumor targets of different etiologic origins and did not kill concanavalin-A-induced lymphoblasts. The broad target-cell reactivity of these AK cells was also confirmed by cold target-inhibition experiments. Generation of AK cell correlated with interleukin-2 (IL-2) production, and the levels of AK cells generation paralleled those of IL-2 production. Furthermore, the generation of AK cells was blocked by the anti-IL-2 receptor monoclonal antibody (MAb) (alpha IL-2R), indicating that IL-2 was involved, and thus these AK cells were lymphokine-activated killer (LAK) cells. We previously showed that the expression of AGM1 on LAK precursors disappeared when they differentiated into LAK effectors, indicating that the activated LAK cells lacked AGM1. When examining the serologic phenotype of the LAK precursors in tumor-bearing hosts, we found that they lacked AGM1, which suggested that these LAK precursors were in an "activated" state. These cells were still Thy1-, and were thus different from fully activated LAK effectors which were Thy1+ cells, indicating that the full differentiation of LAK cells in vivo was arrested in the tumor-bearing hosts. We also found that the presence of small amounts of X-irradiated tumor cells prevented the generation of AK cells. These findings suggest that, in the tumor-bearing hosts, the presence of tumor cells triggers the activation of AK precursors; however, the same tumor cells may also be immunosuppressive, which prevents the full differentiation of AK precursors into AK effectors.
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PMID:Generation of activated killer cells in tumor-bearing hosts. 310 Apr 59


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